Saccharomyces cerevisae plasmid (circumference : 2 pm) that has been engineered to work as a vector in yeast. 3' polyadenylation (3' poly-A tailing) During eukaryotic pre-mRNA processing, an enzyme-driven modification that removes the 3' end of the pre- mRNA and adds numerous adenines. 3'splice site In eukaryotic pre-mRNA processing, the location of cleavage at the 3' end of an intron. Contains an AG dinucleotide in a consensus sequence. 3'to 5'exonuclease activity DNA- and RNA- digesting activity that progresses in the 3' to 5' direction to remove nucleotides. See also DNA proofreading. 3' untranslated region (3' UTR) The untranslated segment of mRNA between the stop codon and the 3' end of the transcript. 5'capping In eukaryotic pre-mRNA processing, the addition of 7-methylguanosine to the nucleotide at the 5' end of pre-mRNA by a triphosphate bridge. Methylation of adjacent nucleotides may also occur. 5'splice site In mRNA processing, the location of cleavage at the 5' end of an intron. Contains a GU dinucleotide in a consensus sequence. 5'to 3'exonuclease activity DNA- or RNA- digesting activity that progresses in the 5' to 3' direction to remove nucleotides. 5'to 3'polymerase activity DNA synthesizing activity of DNA polymerases that progresses in the 5' to 3' direction to add new nucleotides to a growing DNA strand. Requires a template strand. 5' untranslated region (5' UTR) The untranslated segment of mRNA between the 5'end of the tran- script and the start codon. 5-4 photoproduct A DNA lesion and potential mutagenic event caused by exposure to ultraviolet (UV) irradiation. -10 consensus sequence See Pribnow box. 1O-nm fiber The "beads-on-a-string" form of chromatin, in which DNA is wrapped around nucleosomes. 3o-nm fiber A structure of chromatin in which his- tone 1 (H1) partially condenses chromatin fibers into a coiled form. Also known as solenoid or solenoid structure. 30S initiation complex In bacterial translation, the complex formed by a small ribosomal subunit, mRNA, and the tRNA carrying fMet. -35 consensus sequence A specifi.c consensus sequence of the bacterial promoter at which RNA polymerase is bound. 7OS initiation complex The fully assembled bacte- rial ribosome that is prepared to initiate translation. 300-nm fiber A structural state of chromatin in which chromatin fibers are looped and condensed. a-globin gene A gene belonging to a family of closely related genes that encode a globin polypep- tide that is part of hemoglobin. cr-proteobacteria Lineage of bacteria that are the closest extant relatives of the lineage that gave rise to mitochondria. pA allele The common (wild-type) allele of the human B-globin gene. B-globin gene A gene belonging to a family of closely related genes that encode a globin polypep- tide that is part of hemoglobin. ps allele A specific mutant allele of the human B-globin gene that produces sickle cell disease in homozygous individuals. e (theta) structure In bacterial DNA replication, the name given to an intermediate structure of DNA replication of a circular molecule with a single origin of bidirectional replication. e (theta) value A variable indicating a recombination distance between genes. Used in lod score analysis. aberrant ratio In fungi, a ratio of haploid spore geno- types within a single ascus indicating gene conversion. acentric fragment (acentric chromosome) A chro- mosome fragment without a centromere. acrocentric chromosome A eukaryotic chromo- some in which the centromere is very near one end. Forms a chromosome with long and short arms of distinctly different lengths. activator (Ac)element In transposition, a transpos- able genetic element containing a transposase gene. activator binding site DNA sequence to which an activator protein binds to regulate gene expression. Term refers to regulatory sites in bacteria; in eukary- otes, the equivalent sequence would be called an enhancer element. activator protein A transcription factor that binds to regulatory sequences associated with a gene and upregulates that gene's expression. addition rule See sum rule, additive genes Genes contributing to a polygenic trait and producing their effect by their cumulative contributions that are approximately equal for each gene. additive variance (Va) For quantitative traits, the component of genetic variance contributed by genes having an additive effect on phenotypic variance. adenine (A) One of four nitrogenous nucleotide bases in DNA and RNA; one of the two types of purine nucleotides in DNA and RNA. adjacent-l segregation A pattern of chromosome segregation that can occur following reciprocal bal- anced translocation. Leads to gametes carrying gene duplications and deletions. admixed population A population whose members are a blend of formerly distinct populations. agarose An inert material derived from agar that is mixed with buffer and used to form gels for gel electrophoresis. allele An alternative form of a gene. allele-counting method A method for determining allele frequency in a sample by tabulating the number of alleles of each type. allelic phase Describing the cis and trans arrange- ments of alleles of linked genes on homologous copies of a chromosome pair. allelic series A group of alleles of a gene that display a hierarchy of dominance relationship among them. allolactose A modified from of lactose that binds to the lac repressor protein, inducing an allosteric change that reduces the DNA binding ability of the complex. allopatric speciation The development of new species in geographic isolation. allopolyploidy A polyploidy organism arising through the union of chromosome sets from differ- ent species. allosteric domain Domain of a protein that allows the protein to change shape when it binds to a spe- cific molecule; the protein in the new shape is altered in its ability to bind to a second molecule (e.g., DNA). Also known as allostery, allosteric effector compound Molecule that binds to the allosteric protein domain and subsequently induces a change in the bound protein. allostery Reversible interactions of a small molecule with a protein that lead to changes in the shape of the protein and to a change in the interaction of the protein with a third molecule. alternate segregation A pattern of chromosome segregation that can occur following reciprocal bal- anced translocation that leads to the production of viable gametes. alternative mRNA processing (alternative intron splicing, promoters, polyadenylation) In eukary- otic pre-mRNA processing, alternative processes by which different mRNAs can be produced from the same gene using different promoters, polyadeny- lation sites, or by removal of different exon elements. alternative sigma (o) factor Different forms of the sigma subunit of bacterial RNA polymerase that induce distinct conformational changes to the RNA polymerase core and to the recognition of distinct promoters. Ames test A laboratory method commonly used to determine whether a compound or one of its break- down products is mutagenic. amino acid An aminocarboxylic acid that is a com- ponent of a polypeptide or protein. aminoacyl site (A site) The site on a ribosome at which incoming charged tRNAs match their anti- codon sequence with mRNA codons. aminoacyl-tRNA synthetase (IRNA synthetase) A group of enzymes whose specific functions are to identify particular tRNAs and catalyze the attachment of the appropriate amino acid at the 3'terminus. amorphic mutation See null mutation. anagenesis Phylogenetic evolution of a new species from an ancestral species without branching. anaphase The phase of mitosis during which sister chromatids separate (anaphase A) and move to opposite poles (anaphase B). G-1 G.2 GLOSSARY aneuploid An uneven number of chromosomes. Usually the result of the gain or loss of a chromosome-that is,2n + 1 (trisomy) or 2n - | (monosomy). annotation (gene annotation, genome annota- tion) The process of attaching biological functions to DNA sequences. Genome annotation is the process of identifying the location of genes and other functional sequences within the genome sequence; gene annotation defines the biochemical, cellular, and biological function of each gene product the genome encodes. Antennapedia complex One of two homeotic gene clusters in Drosophila consisting of five genes (labial, Deformed, Sex combs reduced, proboscipedia, and Antennapedia) that act in combination to specify the cephalic and thoracic parasegments. anticodon The nucleotide triplet sequence of trans- fer RNA that pairs with an mRNA codon sequence in translation. antiparallel Opposite 5'and 3'orientations of two complementary nucleic acid strands. antisense RNA An RNA molecule that is comple- mentary to a portion of a specific mRNA. antitermination stem loop A stem loop that allows RNA polymerase to continue transcription through the leader region of bacterial attenuator controlled operons and into the structural genes of an operon (e,g.,the2-3 stem loop in trp operon regulation). apurinic site The location of a nucleotide that has lost its purine base. arabinose(ara) operon An inducible operon consist- ing of genes encoding enzymes allowing the use of ara- binose as a carbon source. The operon is controlled by a single regulatory protein, which carries out both positive and negative transcriptional regulation. Archaea One of the three domains of life; separate from Bacteria and Eukarya. Argonaute Protein subunit of RISC (RNA-induced silencing complex) that binds small RNA molecules and provides either the catalytic "slicer" activity or the translational repressor activity. artificial cross-fertilization A controlled cross between plants made by an investigator who trans' fers pollen from one plant to fertilize the other plant. ascus The spore sac formed by fungi containing four (tetrad) or eight (octad) haploid spores. Also called spores. aster The structure forming during cell division that contains microtubules emanating from centrosomes. attachment site (att site) Identical or nearly identi- cal sequences on the bacterial and bacteriophage chromosomes that are cut and used to integrate or to excise the bacteriophage chromosome from the bacterial chromosome. attenuation A gene regulatory mechanism that fine-tunes transcription to match the momentary requirements of the cell, achieving a more or less steady state of compound availability. attenuator region A regulatory region downstream of the promoter of repressible amino acid operons that exerts transcriptional control (in the form of I transcription termination) based on the translation of a leader peptide, the efficiency of which is deter- mined by the availability of specific amino acids. autonomous transposable element A transposable genetic element that encodes transposase and can initiate its own transposition. autopolyploidy A pattern of polyploidy produced by the duplication of chromosomes from a single genome. autoradiograph A photographic image obtained by exposure of X-ray film to the radioactive decay of isotopes attached to molecular probes. Used in the analysis of gel electrophoresis, autosgmal dominant inheritance A pattern of hereditary transmission in which the dominant allele of an autosomal gene results in the appearance of the dominant phenotype. autosomal inheritance Hereditary transmission of genes carried on autosomes. autosomal recessive inheritance A pattern of hereditary transmission in which the recessive allele of an autosomal gene results in the appearance of the recessive phenotype. Bacteria One of the three domains of life; separate from Archaea and Eukarya. bacterial artificial chromosome (BAC) Cloning vec, tor used in bacteria that utilizes the F plasmid origin of replication; can accept DNA inserts up to 500 kb. bacterial chromosome The main, usually singular, chromosome encoding the genome of a bacterium. bacteriophage (phage) A virus whose host is a bacterium. balanced polymorphism A genetic polymorphism maintained in a population because organisms with the heterozygous genotype have higher relative fitness than do organisms with either of the homozy- gous genotypes. balancer chromosome A chromosome with inversions used to maintain specific allele combina- tions (u.9., recessive lethal alleles) in genetic stocks. band (in electrophoresis gel) A region in an elec- trophoresis gel or in an autoradiograph where a pro- tein of nucleic acid congregates. Usually visualized using a stain or molecular probe. barcode Short DNA sequences that identify specific strains in knockout libraries. Barr body The darkly staining inactive X chromo- some visible in mammalian female nuclei. The result of random X inactivation. base analog A compound with structure similar to a naturally occurring nucleotide base that can substi- tute for the base in DNA. base-pair substitution mutation A DNA sequence change resulting in the substitution of one base pair for another. base stacking A phenomenon of DNA base-pair interaction that rotates the base pairs around a cen- tral axis of symmetry and imparts twisting to the double helix. basic local alignment search tool (BLAST) A com- puter program designed to search for homologous sequences in databases. bidirectional DNA replication The standard method of DNA replication that synthesizes new DNA in both directions from a replication origin. binomial probability A probability function using two coefficients, a and b, whose sum equals 1 and whose products predict the probability of events. bioinformatics The use of computational approaches to decipher DNA-sequence information. biosynthetic pathway A multistep biochemical pathway that synthesizes an end product or compound. biparental inheritance Condition in organellar inheritance where both parental gametes make con- tributions of cytoplasmic organelles to the zygote; contributions are often unequal because one gamete contributes more of the cytoplasm and the other gamete makes a smaller contribution. bithoraxcomplex One of two homeotic gene clusters in Drosophila consisting of three genes (U lt r ab ith o r A n, ab d o m in al - A, and Ab d o m i n al - B) that act in combination to specify the thoracic and abdominal parasegments. blending theory of heredity An obsolete theory of heredity proposing that the traits of offspring are the average of parental traits. blotting (in gel electrophoresis) The process of transferring proteins or nucleic acids from an elec- trophoresis gel to a permanent membrane or filter. blunt ends 5' or 3' ends of double-stranded DNA lacking any single-stranded overhangs. branch point adenine In intron splicing, an adenine nucleotide near the 3' splice site of an intron that joins with a guanine located at the 5' splice site by a 2'-to-S' phosphodiester bond to form a lariat intron. BRCAl -associated genome surveillance complex (BASC) A multiprotein complex that surveys the genome for mutations at the G1- to S-phase cell cycle checkpoint. broad sense heritability (H2l The proportion of total phenotypic variance that is contributed by total genetic variance. bulky adduct Large chemical groups added to nucleotides by alkylating agents. bypass polymerase A group of DNA polymerases that are unstable and synthesize short regions of DNA under conditions in which the main DNA poly- merase is unable to function, such as when faced with DNA lesions that block replication. Also called translesion DNA poly merase. CAAT box A common consensus sequence compo- nent of eukaryotic promoters. CAP (catabolite activator protein) In bacterial transcription regulation, binds cAMP (cyclic AMP) at low glucose concentrations to positively regulate the transcription of operons that allow the use of alternative carbon sources. CAP binding site A bacterial DNA regulatory sequence to which the CAP-cAMP complex binds to positively regulate gene expression. See also CAP-cAMP complex, CAP-cAMP complex Formed by joining catabolite activator protein to cAMB the complex binds to the CAP binding site of the bacterial lac promoter to reg- ulate gene expression. catabolite repression Situation where the presence of the preferred catabolite (e.g., glucose) represses the transcription of genes for an alternative catabolite (e.9., lactose). Cdks (cyclin-dependent kinases) A group of multimeric proteins whose levels fluctuate during the cell cycle. Composed of cyclin proteins and protein kinases, Cdks control entry and progression through mitosis. cell cycle Consisting of interphase (G1phase, S phase, and G2phase) and M phase (mitosis or meiosis) in cells. The transition from one phase to the next is controlled by protein-based interactions. cellular blastoderm Stage of Drosophila embryogenesis in which the nuclei are located at the periphery of the embryo and are enclosed by cell membranes. central dogma of biology The description of the functional relationship between DNA, RNA and pro- teins (DNA to RNA to protein). centromere A specialized DNA sequence on eukaryotic chromosomes that is the site of kineto- chore protein and microtubule binding. Gentrosome A cytoplasmic region, containing a pair of centrioles in many eukaryotic species, from which the growth of microtubules forms the spindle appara- tus during cell division. chaperone A category of eukaryotic proteins that assist with the folding or movement of other polypeptides. Chargaff's rule The observation that the percentage of adenine equals that of thymine and that guanine percentage equals cytosine percentage in DNA. charged IRNA A IRNA to which the correct amino acid has been attached. chiasma (plural: chiasmata) Points of contact between homologous chromosomes that are coinci- dent with crossover locations between the homologs. chi-square test (X2 test) A statistical test to compare the observed results of an experiment with the results predicted by chance. chloroplast An organelle, bounded by a double membrane, where photosynthetic reactions convert light energy and CO2 into fixed organic carbon. chromatin The complex of nucleic acids and pro- teins that compose eukaryotic chromosomes. chromatin modifier Proteins that chemically mod- ify histone proteins in the nucleosomes by adding or removing specific chemical groups, thereby modifying chromatin structure and regulating gene expression. chromatin remodeler Proteins that reposition nucleosomes within chromatin in such a way as to open or close promoters and other regulatory sequences or that change the composition of nucleosomes, altering their biological activity (e.9., S!flIlSNF, IS'W.I, S\)fRl). chromatin remodeling Processes that modify the structure or composition of chromatin. Usually asso- ciated with alterations of nucleosome binding to DNA and affecting the regulation of gene transcription. chromatography A technique for separating the components of a molecular mixture by their similari- ties and differences. chromosome A structure composed of DNA and associated proteins that in total contain the genome of an organism. chromosome aberration An abnormality of chro- mosome number or structure. chromosome arms fiong arm (q arm), short arm (p arm)] The segments of eukaryotic chromosomes between the centromere and the telomeres. chromosome banding A group of laboratory methods that stain eukaryotic chromosomes to reveal distinctive patterns of light and dark bands. Chromosome banding by Giemsa staining produced standardized patterns for different chromosome of selected species. Also known as Giemsa, (G) banding. chromosome break point The location of a chro- mosome break. chromosome fusion See Robertsonian translocation, chromosome inversion (paracentric, pericentric) A structural alteration of a chromosome in which a segment breaks away from the chromosome and sub- sequently reattaches after 180" rotation. See also inv ersio n heterozygote. chromosome scaffold Composed of numerous nonhistone proteins, the superstructure of eukaryotic chromosomes. chromosome territory The region within a nucleus occupied by a particular chromosome during interphase. chromosome theory of heredity The theory developed in the early 20th century that genes are carried on chromosomes and that the meiotic behavior of chromosomes is the physical basis of Mendel's laws. chromosome translocation The relocation of a chromosome or chromosome segment to a non- homologous chromosome. chromosome walking See positional cloning, cis-acting Acting on the same chromosome (e.g., DNA sequences that control expression of genes encoded on the same piece of DNA). cis-acting regulatory sequence Sequences to which proteins bind to regulate transcription of genes located on the same chromosome as the sequences. cis-dominant The principle that the operator can influence only the transcription of adjacent downstream genes. clade In phylogenetics, a group of organisms defined by characteristics that are unique to the group and distinguish the group from others. cladistics The classification of organisms by charac- teristics that are unique to the group and distinguish it from other groups. Involves branching of new species from ancestral species. See also clade. cladogenesis Phylogenetic evolution by branching of descendant species from ancestral species. clamp loader A multiprotein complex that pairs with DNA polymerase and the sliding clamp during replication. clone-by-clone sequencing An approach to genome sequencing where each chromosome is first broken into overlapping clones that are then arranged in linear order to produce a physical map of the genome. Each clone in the map is then sequenced separately. Contrast with who le-genome shotgun sequencing. closed chromatin Chromatin in which regulatory DNA is covered by nucleosomes, thus restricting the access of regulatory proteins to the sequences ren- dering genes in closed chromatin transcriptionally silent. closed promoter complex The initial stage of tran- scription that forms when RNA polymerase loosely binds the promoter. coding strand The nontemplate strand of DNA that has the same 5'-to-3' polarity as its transcript and the same sequence, except for t in DNA and u in RNA. codominance The equal and detectable expression of both alleles in a heterozygous organism. codon The nucleotide triplet of mRNA that encodes a single amino acid. (odon bias The preferential use of specific codons where there is redundancy in encoding a specific amino acid. G LOSSARY G.3 coefficient of coincidence (c) The ratio of the observed number of double recombinants to the number of double recombinants expected to occur by chance. coefficient of inbreeding (F) The probability that two alleles carried in an individual are homozygous identical by descent (IBD). cohesive (cos) ends Short, single-stranded over- hangs at 5' and 3' ends produced after digestion with certain restriction ends. The cohesive ends are termed compatible if they can base-pair with complementary single-stranded ends of another DNA molecule. Compare with cohesive sites. cohesive (cos) sites The single-stranded ends of phage lambda that facilitate circularization or con- catamerization of lambda phage genomes and that interact with coat proteins during packaging of phage particles. Compare with cohesive ends. cointegrate In replicative transposition, the fusion of two circular transposable elements into a single, larger circular element. comparative genomics See evolutionary genomics. Gompensatory mutation A second mutation occurring at another site that fully or partially restores wild-type function lost when an initial mutation occurs. complementary base pairs The specific pattern of purine-pyrimidine pairing of nucleic acid strands. In DNA, e with c and A with r; RNA uses u instead of r. complementary DNA (cDNA) library Collection of DNA clones, originally derived via reverse transcrip- tion of mRNA molecules into DNA (cDNA) and cloned into a vector. complementary gene interaction (927 ratio) A characteristic ratio of phenotypes produced by the interaction of two complementary genes that control a trait. complementation group A group of mutations that affect the same gene. complete genetic linkage The absence of crossing over between linked genes. complete initiation complex The multisubunit complex that forms at the promoter immediately before the onset of transcription. Gomposite transposon In bacteria, a transposable element containing multiple genes located between terminal insertion sequences. concordance In twin studies, the observation that both twins exhibit the trait. conditional probability A probability prediction that is dependent on another previous event having taken place. conjugation The short-term union of two bacterial cells for the unidirectional transfer of DNA from the "donor" to the "recipientl'The transferred material may be plasmid DNA or donor bacterial chromo- some DNA. conjugation pilus The hollow filament extending from the donor bacterium to the recipient bacterium through which DNA is transferred. Also known as conjugation tube. conjugation tube See conjugation pilus. consanguineous mating See inbreeding, consensus sequences A nucleotide sequence in a DNA segment derived by comparing sequences of similar segments from other genes or organisms. G-4 GLOSSARY The most commonly occurring nucleotides at each position comprise the sequence. conservative DNA replication A disproven model of DNA replication positing that one duplex pro- duced by replication contained the two original strands and the other two daughter strands. conservative transposition In transposition, the removal of a transposable element from one location followed by insertion into a new location. conserved noncoding sequence (CNS) Sequences that do not code for amino acids and are conserved across significant phylogenetic distances. constitutive heterochromatin Chromosome regions containing chromatin that is always densely compacted. Usually containing highly repetitive DNA sequences. constitutive mutants Mutants in which a gene is always expressed rather than being under regulatory control. constitutive transcription State in which a gene is continuously transcribed. contiguous sequence (contig) Overlapping DNA clones that together cover an uninterrupted continu- ous stretch of DNA sequence. continuous variation In polygenic and multifacto- rial traits, the observation of phenotypic distribution over a continuous range. controlled genetic cross Genetic crosses controlled by an investigator who usually knows the genotypes and/or phenotypes of the organisms being crossed. convergent evolution Processes of independent evolution of similar structures in unrelated species. Also known as homoplasmy. co-option A common theme in the evolutionary history of genes bywhich genes and genetic modules are reused in a new manner to direct the patterning or growth of novel organs. coordinate genes Genes, often with maternal effects, that establish the major axes of the embryo, especially the anterior-posterior and dorsal-ventral axes; examples include bicoid and nanos. copy number variant (CNV) A specific type of structural variant due to insertions or deletions (indels) greater than 1 kb in length. core DNA The approximately 146 base pairs of eukaryotic DNA that wrap each nucleosome. core element Consensus sequences in the active regions of promoters recognized by RNA polymerase I. core enzyme The five-polypeptide component of bacterial RNA polymerase that actively carries out transcription. corepressor An accessory molecule required for a repressor protein to exert its function. cosmid vector Cloning vector used in bacteria that utilizes phage lambda cos sites for packaging of phage and a bacterial origin of replication for subsequent maintenance in bacteria; can accept DNA inserts of up to 40 kb. cosuppression The silencing, via a small RNA mediated mechanism, of an endogenous gene due to the presence of a homologous transgene or virus. Cosuppression can occur at the transcriptional or post-transcriptional level. cotransduction The simultaneous transduction of two or more genes contained on a donor DNA fragment into a recipient cell, where it undergoes homologous recombination to be spliced into the transductant chromosome. cotransduction frequency The frequency with which two genes are transduced. cotransduction mapping A method of mapping donor bacterial genes based on their frequency of cotransduction. cotransformation Simultaneous transformation of two or more genes carried on a donor DNA fragment into a recipient. covered promoter Promoter in which nucleosomes are found adjacent to the transcription start site, pre- venting efficient transcription initiation. This feature is common at highly regulated genes. CpG dinucleotide See CpG island. CpG island Region in which the frequency of CpG dinucleotides is higher than the average for the genome; commonly found near the transcription start sites of animal genes. The cytosines are often methylated when the gene is inactive and demeth- ylated when the gene is transcriptionally active. crossing over The breakage and reunion of homologous chromosomes that results in reciprocal recombination. crossover suppression The significant reduction, or complete absence, of progeny with recombinant chromosomes due to duplications and deletions of genetic material following crossing over within the inversion loop in organisms that are heterozygous for an inversion. cryptic splice site A 5' or 3'splice site that is not nor- mally used except when a mutation either inactivates an authentic splice site or creates a new splice site at the cryptic site location. See also splicing mutation, cyanobacteria Lineage of photosynthetic bacteria that are the closest extant relatives of the lineage that gave rise to the plastids. cyclin protein A family of proteins whose levels fluctuate during the cell cycle. Cyclins pair with protein kinases to form cyclin-dependent kinases (Cdks) that help regulate the cell cycle. cytokinesis Part of telophase, the process of cyto- plasmic division between daughter cells. cytological markers Structural differences between homologous chromosomes that serve to differentiate the chromosomes when they are visualized using microscopy. cytoplasmic inheritance (organellar inheritance) The transmission of genes on mitochondrial and chloroplast chromosomes; genes that are located in the cytoplasmic organelles as opposed to the nucleus. cytosine (C) One of four nitrogenous nucleotide bases in DNA and RNA; one of the two types of pyrimidine nucleotides in DNA and RNA. daughter cell The genetically identical cells pro- duced by mitotic cell division. daughter strand A newly synthesized strand of DNA that is complementary to a template strand. deamination A DNA lesion resulting in the loss of an amino group (NHr) from a nucleotide base. degrees of freedom (df) The number of independent variables in an experiment. In a chi- square test, most often the number of outcome class minus l(n-l). delayed age of onset The appearance of an abnormal phenotype that is not present at birth but appears later in life and is caused by an inherited mutation. deletion The loss of genetic material (see also interstitial, microdeletion, partial deletion, partial deletion heterozygote, terminal deletion), deletion mapping A,method for mapping genes utilizing partial chromosome deletions with known locations to expose recessive mutants by pseudodominance. denaturation In DNA, the separation of complementary strands of nucleic acids by hydrogen bond breakage. In polypeptides and proteins, the unfolding of tertiary or quaternary structures. densitometry A technique for passing Iight through an electrophoresis gel to detect the presence of a stained band of protein or nucleic acid. deoxynucleotide monophosphates (d NMps) Monophosphate forms of deoxynucleotides. deoxynucleotide triphosphates (dNTps) Triphosphate forms of deoxynucleotides. deoxyribonucleic acid (DNA) The hereditary mole- cule of organisms. Composed of two complementary strands of nucleotides with purine bases adenine (A) and guanine (G) and pyrimidine bases thymine (T) and cytosine (C). depurination A DNA lesion occurring when a deoryribose molecule loses its purine nucleotide base. See apurinic site. dicentric bridge In a dicentric chromosome, the portion between the two centromeres that are drawn to opposite poles of the cell during division. dicentric chromosome A chromosome with two centromeres. dicer Ribonuclease that acts on double-stranded RNA responsible for the generation of small regula- tory RNA molecules, such as microRNAs and small interfering RNAs; typically 2L-30 nucleotides in length. dideoxy DNA sequencing A method of DNA sequencing devised by Fred Sanger that uses a mixture of deoxynucleotide and dideoxynucleotide triphosphates to selectively block DNA replication, producing a ladder of partially synthesized DNA strands of different lengths. Also known as the Sanger method. dideoxynucleotide triphosphates (ddNTps) Rare DNA nucleotides absent oxygen molecules at the 2' and the 3'carbons that are most commonly used in dideoxynucleotide DNA sequencing. differential reproductive fitness. See relative fitness. differentiation Process by which cells become restricted in their developmental potential and take on specialized morphologies and physiological activities. dihybrid cross A cross between organisms that are heterczygous for two loci. diploid number of chromosomes (2n) The characteristic number of chromosomes in somatic cell nuclei of diploid species. Equal to twice the haploid (n) number of chromosomes found in the nuclei of gametes of sexually reproducing diploid species. direct repeat Identical or nearly identical DNA sequences in the same orientation that are separated by intervening DNA. directionalcloning Technique whereby a DNA inser! is cloned with a specific directionality with respect to / sequences of the cloning vector; usually accomplished by using two different restriction enzymes. directional natural selection See directional selection, directional selection Natural or artificial selection that continuously changes the frequency of an allele in a direction toward fixation (frequency - 1.0) or toward elimination (frequency : 0.0). discontinuous variation A phenotype distribution containing discrete or separable categories. discordance In twin studies, the observation that the traits exhibited by the twins are different. disjunction The normal process separation of homologous chromosomes or of sister chromatids during cell division. dispersive DNA replication A disproven model of DNA replication positing that each strand of daugh- ter duplexes is composed of segments of original DNA and segments of newly synthesized DNA. displacement loop (D loop) During DNA damage repair and homologous recombination, the displace- ment of a single strand of DNA by strand invasion. disruptive selection Natural or artificial selection of phenotypic extremes in a population, leading eventu- ally to two strains with distinctive phenotypes. dissociation (Ds) element In transposition, a non- autonomous genetic element that is incapable of transposing on its own. DNA-binding protein A general term for a protein that binds to DNA; the interaction can be either DNA-sequence specific (most regulatory proteins) or DNA-sequence nonspecific (e.g., structural proteins such as histones). DNA clone A fragment of DNA that is inserted into a vector, such as a plasmid, cosmid, or artificial chromosome. DNA double helix (DNA duplex) The two complementary strands of DNA arranged in antipar- allel orientation. DNA library Collection of DNA clones in which the DNA is usually derived from a single source. DNA ligase An enzyme active in DNA replication that joins together segments of a DNA strand by catalyzing formation of a phosphodiester bond. DNA loop In gene regulation, a condition where the DNA sequences between regulatory elements form an extended loop that allows distant regulatory sequences with associated DNA-binding proteins to interact. DNA microarray Collections of synthesized DNA fragments attached to a solid support and represent- ing sequences present in a genome; can be used to assess transcription patterns, transcription factor binding sites, and recombination patterns, among other uses. DNA nucleotides DNA building blocks composed of deoxyribose sugar, a nitrogenous base, and one or more phosphate groups. See also adenine (A), thymine (T), cytosine (C), and guanine (G). DNA polymerase (pol l, pol ll, pol lll) The large multisubunit complex responsible for the synthesis of new strands of DNA during DNA replication or DNA repair. DNA proofreading The capacity of many types of DNA polymerase to utilize a 3'to 5'exonuclease activity to remove and replace mismatched or dam- aged nucleotides during replication. See also 3'to S' exonuclease activity. DNA replication The synthesis of new DNA strands by complementary base pairing of nucleotides in a daughter strand to those in a template strand. DNasel hypersensitive site Regions of chromatin sensitive to cleavage by DNase I; these often represent open chromatin that is transcriptionally active. DNA transposon One type of transposable genetic element encoding a transposase and capable of transposition. DNA triplet Three DNA nucleotides corresponding to a codon of mRNA. dominance varianG In polygenic and multifacto- rial inheritance, the portion of genetic variance attributed to the dominance effects of contributing genes. dominant epistasis (12:3:1 ratio) A characteristic ratio of phenotypes produced by the interaction of two genes that control a trait in which a dominant allele of one gene masks or reduces the expression of alleles of a second gene. dominant interaction (9:6:1 ratio) A characteristic ratio of pheno{pes produced by the interaction of two genes that control a trait in which the presence of dominant alleles of both genes produces one phe- notype, one dominant allele of either gene produces a second phenotype, and organisms with only recessive alleles for the interacting genes have a third phenotype. dominant negative mutation A dominant muta- tion that behaves as a loss-of-function, often due to blocking the formation or normal function of a mul- timeric protein complex. dominant phenotype The phenotype observed in a heterozygous organism that is identical to the phe- notype observed in a homozygote. The phenotype produced when an organism is homozygous for the dominant allele or carries a single copy of the domi- nant allele in the heterozygous genotype. Compare with recessive phenotype. dominant suppression (13:3 ratio) A characteristic ratio of phenotypes produced by the interaction of two genes that control a trait in which the dominant allele of one gene suppresses the expression of the dominant allele of the second gene. donor cell (bacterial donor) The bacterial cell that is the source of DNA transferred to a recipient cell by either conjugation, transduction, or transformation. donor DNA DNA to be used in cloning or other recombinant DNA technologies. dosage compensation A mechanism for equalizing the expression of X-linked genes in males and females of a species. double Holliday junction (DHJ) An intermediate structure temporarily connecting chromatids of homologous chromosomes that forms during homol- ogous recombination. double recombinant (double crossover) The occurrence of two crossovers between homologous chromosomes in a particular region. May involve two, three, or all four chromatids. double-strand break repair Following phosphodi- ester bond breakage on both strands of a DNA duplex, a mechanism of DNA damage repair. Related to the mechanism for homologous recombination. downstream Referring to a gene or sequence location that is toward the 3' direction on the coding strand. drosha Ribonuclease that processes pri-microRNA molecules into pre'microRNA molecules in animals. duplicate gene action (15:1 ratio) A characteristic ratio of phenotypes produced by the interaction of GLOSSARY G-5 two genes that duplicate each other's action due to genetic redundancy. duplication The gain of genetic material by the inclusion of one or more additional copies of a chro- mosome segment. See also microduplication, partial dup li c at i o n, and p ar ti al dup lic atio n h eter o zy go te, early genes The first genes expressed following the infection of bacterial cells by bacteriophage. The fate of early gene expression determines whether the phage undergoes the lytic cycle or the lysogenic cycle. early promoters Regulatory sequences responsible for the activation of early genes or operons in bacteriophage. East-West (EW) resolution One of the possible pat- terns for resolving a Holliday junction to separate homologous chromosomes before meiotic anaphase. electrophoretic mobility A measurement of (1) the distance of migration or (2) the speed of migration of a nucleic acid or protein in gel electrophoresis. elongation factor (EF) A group of proteins associ- ated with ribosomes that contribute to the elongation of the polypeptide product. embryonic stem cells In vertebrates, totipotent cells of early embryos that can give rise to any and all cell types of the organism. endosymbiont An organism that lives within the body or cell of another organism. endosymbiosis An (often) mutually beneficial relationship between organisms in which one organism, the endosymbiont, inhabits the body of the other. endosymbiosis theory Hypothesis that the mitochondrion and chloroplast are evolutionarily derived from bacterial endosymbionts related to extant u-proteobacteria and cyanobacteria, respectively. enhanceosome Protein complex that binds enhancer elements and directs DNA bending into loops that bring the protein complex into contact with RNA polymerase and transcription factors bound at the core promoter or with protein complexes bound to proximal promoter elements. enhancer A eukaryotic cis-acting DNA regulatory sequence to which trans-acting factors bind and stimulate transcription. See also enhancer sequence. enhancer screen A genetic screen designed to iden- tify mutations in genes that worsen the phenotypic effects of mutations in another gene. enhancer sequence Sets of regulatory sequences that bind specific transcriptional proteins that can elevate transcription of targeted eukaryotic genes. enhancer trap A transgenic construct inserted ran- domly into the genome that allows identification of enhancer elements controlling specific patterns of gene expression. environmental variance (t/g) For quantitative traits, the proportion of the total phenotypic variance contributed by differences in the environment expe- rienced by population members. epigenetic Heritable patterns or changes in gene expression that are not associated with any change in DNA sequence. epigenetic marks A collection of chemical marks and modifications, such as acteylation and methyla- tion of histone proteins, that are functional in chromatin remodeling. Also known as epigenetic modif.cation. G.6 G LOSSARY epigenetic modification Chemical modifications of DNA or associated histones, such as acetylation and methylation, that alter chromatin structure and influ- ence gene transcription. epistasis See epistatic interaction. epistatic interaction A group of specific patterns of gene interaction in which an allele of one gene modi- fies or prevents the expression of alleles of another gene. Also known as epistasis. equilibrium frequency The stable frequency of an allele in a population attained and maintained through the action of evolutionary processes. ethidium bromide (EtBr) A compound used to stain DNA and RNA in electrophoresis gels. euchromatic region See euchromatin. euchromatin Chromosome regions containing chro- matin that is not densely compacted. Most expressed genes are located within euchromatic regions of chro- mosomes. Also known as euchromatic region. Eukarya One of the three domains of life; separate from Archaea and Bacteria. See also eukaryote. eukaryote Referring to organisms belonging to the domain Eukarya. eukaryotic initiation factor (elF) A group of eukaryotic proteins that associate with ribosomal subunits and help initiate translation. euploid A number of chromosomes that is an exact multiple of the haploid number. E(var) mutations Mutations that enhance position effect variegatio n in Drosophila. Mutated genes produce proteins that are active in chromatin remodeling. evo-devo The study of the evolution of development. evolution (1) Any change in the genetic characteris- tics of a population, strain, or species over time. (2) The theory that all organisms are related by com- mon ancestry and have diversified from common ancestors over time. evolutionary genetics The study of evolution and evolutionary processes using genetic techniques and tools. evolutionary genomics The comparison of genomes, both within and between species. It illumi- nates the genetic basis of similarities and differences between individuals or species. evolutionary processes Four processes-natural selection, migration, mutation, and random genetic drift-that can cause changes in the genetic charac- teristics of a population or lineage. exconjugant cell The cell that is the product of con- jugation between a donor cell and a recipient cell. exit site (E site) On the ribosome, the site through which an uncharged tRNA exits. exon A nonintron segment of the coding sequence of a gene. )oined together following intron splicing, exons correspond to the mRNA sequence that is translated into a polypeptide. exonic splicing enhancers (ESEs) Exon sequences that play a role in intron splicing. expression array DNA microarray that carries unique sequences from every annotated gene of the genome and is used to monitor gene expression patterns. expression vector Cloning vector possessing DNA sequences required for DNA fragments inserted into the vector to be transcribed and translated. Vectors with sequences facilitating expression in eukaryotes are called eukaryotic expression vectors. F (fertility) factor The plasmid containing genes that confer the ability to act as a donor cell on a bac- terium. May be either an extrachromosomal plasmid or may be incorporated into the donor bacterial chromosome. Also known as F plasmid, F' cell (F' donor) An extrachromosomal fertility plasmid into which a portion of the donor bacterial chromosome has been incorporated. F plasmid. See F (fertility)factor. F*cell (F*donor) A donor bacterium containing an extrachromosomal fertility plasmid. F, generation (first filial generation) The first gen- eration of offspring. In genetic experiments, usually the offspring produced by crossing pure-breeding parents. F, generation (second filial generation) The second generation, produced by crossing F1 organisms. F, generation (third filial generation) The third generation, produced by crossing F2 organisms. facultative heterochromatin Heterochromatic chromosome regions whose level of compaction can vary. Often contains repetitive DNA, but may also con- tain some expressed genes. first-division segregation In Neurospord, and other organisms forming an ascus, the separation of alleles at the first meiotic division due to no crossing over having occurred. fluorescent in situ hybridization (FISH) A labora- tory method for identifying genes or DNA sequences using molecular probes labeled with a compound that can emit fluorescent light upon excitation. forked-line diagram A method for diagramming the probabilities of outcomes in a branching format. forward genetic analysis The classical approach to genetic analysis whereby genes are first identified by mutant phenotypes caused by mutant alleles and the gene sequence is subsequently identified by recombi- nant DNA technologies. AIso known asforward genetics, forward genetics See forward genetic analysis. forward mutation A mutation that alters a wild type and generates a mutant. Also known as mutation. forward mutation rate (F) The frequency of mutation from wild-type alleles to mutant alleles. founder effect The random occurrence of allele and genotype frequency differences between a new popu- lation established by a small number of founders and the larger parental population. four-strand double crossover Two crossover events between a pair of homologous chromosomes that involve all four chromatids. frameshift mutation The insertion or deletion of DNA base pairs resulting in translation of mRNA in an incorrect reading frame. frequency distribution A visual display or his- togram of quantitative data. functional domain A protein region with a specific function or interaction. functional genomics Using genomic sequences and genome-wide patterns of transcripts and protein expression to understand gene function in an organism. functional RNAs Various types of transcripts that are not translated and are functional as nucleic acids. See also iRNA, rRNA, snRNA, miRNA, siRNA, ribozymes. fusion gene A recombinant gene comprised of DNA sequences from more than one source (e.g., the \ codon sequences derive\d from one gene and the sequences responsible for elpression derived from a secondgene). \ fusion protein A recombinant protein encoded by DNA sequences from more than one source; made by combining the open reading frames of two unrelated genes. Go The "G zero" phase of the cell cycle, an alternatiye to G1 of the cell cycle entered by mature cells that generally do not divide again until they die. Compare with G7 and G2phase. G, phase The "Gap 1" phase of the cell cycle during which genes are actively transcribed and translated and cells carcy out their normal functions. Compare with Gs and G2 phase. G, phase The "Gap 2" phase of the cell cycle during which the cell prepares to divide. Compare with G6 and G r. gain-of-function mutation A mutation causing a gene to be overexpressed, to be expressed at the wrong time, or to encode a constitutively acting protein. Usually inherited as a dominant mutation. gametes The reproductive cells produced by male and female reproductive structures; sperm or pollen in male animals and plants, and eggs in females. gap genes In Drosophila, genes that control development in large contiguous regions along the anterior-posterior axis; examples inclu de hunchback, giant, krilppel, and knirps. Gaussian distribution See normal distribution. GC-rich box An occasional upstream consensus sequence of eukaryotic promoters that is rich in guanine and cytosine. gel electrophoresis A laboratory method for separating proteins or nucleic acid molecules or fragments using electrical current in a gel matrix. gene The physical unit of heredity, composed of a DNA sequence that is transcribed and encodes a polypeptide or another functional molecule. gene conversion Repair of mismatched (non- complementary) DNA nucleotides in heteroduplex DNA that forms during meiotic recombination. One allele is switched for another allele already in the genotype. gene dosage The number of copies of a gene. gene-environment interaction Interactions taking place between particular genes and specific environ- mental factors. gene family A group of genes that is evolutionarily related via successive gene duplication events that are followed by diversification. gene interaction Referring to genes that interact with one another due to their participation in the production of a particular product or trait. gene knockout Loss-of-function allele of a gene usually obtained via a reverse genetic approach. gene pool The to(al of all alleles present in breeding members of a population at a given moment. gene therapy The use of genes as therapeutic agents to cure or alleviate symptoms of a genetic disease. generalized transducing phage In transduction, a bacteriophage that carries a random segment of the chromosome of a donor cell to the recipient cell. generalized transduction The transduction of a random segment of a donor chromosome into a recipient cell by a transducing phage. See also general ize d tran s ducing p h age. genetic bottleneck A period or event character- izedby a substantial random reduction in popula- tion size. Loss of genetic diversity and allele frequency changes usually occur. genetic chimera A tissue or organism comprised of cells of two or more distinct genotypes. genetic Gode The universal set of correspondences of mRNA codons to amino acids. Used in translation to synthesize polypeptides. genetic complementation (1) The observation of a wild-type phenotype in an organism or cell contain- ing two different mutations. (2) The cross of two pure-breeding mutants that yields progeny that are exclusively wild type. genetic dissection The use of mutations and recombinants in genetic analyses to identify and assemble the genetic components of a biological property or process. genetic drift A process of evolution referring to random changes in allele frequencies that result from sampling errors. Occurs in all populations but is strongest in small populations. genetic fine structure The method of high- resolution analysis of intragenic recombination to map genes at the nucleotide level. genetic heterogeneity The observation of the same phenotype produced by mutation of any one of two or more different genes. genetic liability See threshold of genetic liability. genetic linkage The result of genes being located so near one another on a chromosome that their alleles do not assort independently. Identified by detecting certain pairs of alleles (parentals) that are transmitted together significantly more often than expected by chance and of other pairs of alleles (nonparentals or recombinants) that are transmitted together signifi- cantly less often than expected. genetic linkage mapping Process for creating maps of genes based on their linkage relationships to other genes. genetic markers Alleles of either expressed genes or non-coding chromosomal regions identifying a spe- cific region of a chromosome. Can be used to trace or identify another gene, the chromosome, or a cell, organ, or individual. genetic network Set of interacting genes identified from double mutants or other analyses indicating gene interaction. genetic redundancy The situation where the func- tions of one gene are compensated for by the actions of another gene. genetic screen A procedure whereby a population of organisms is mutagenized and their progeny are propagated and examined for mutant phenotypes. Also known as mutagenesis. genetic variance (Vc) In polygenic and multifacto- rial inheritance, the proportion of total phenotypic variance contributed by genetic variation. genome The entire complement of DNA sequences in a chromosome set of an organism. genome-wide association studies (GWAS) Association analysis performed using genetic marker genes distributed throughout the genome. Designed to locate genes that may influence the variation of quantitative traits. genomic imprinting Epigenetic phenomena that create differential expression of alleles depending on whether they were maternally or paternally inherited. genomic library A set of clones consisting of the DNA representing the genome of an organism. genotype (1) The genetic composition of an organ- ism or a cell (i.e., all the alleles of all the genes). (2) The alleles of a single gene or a specified set of genes in a cell or organism. genotype proportion method A method for estimating allele frequencies in a population by manipulation of genotype frequencies. genotypic ratio (1:2:1 ratio) (1) A ratio or set of rel- ative proportions between organisms with different genotypes. (2) The ratio of Il4 : Ll2 :1/4 observed among the homozygous and heterozygous F2 progeny of a monohybrid cross. germinalgene therapy Gene therapy aimed at cor- recting the genetic defect in the germ cells, such that progeny would not inherit the genetic defect. germ-line cell See gametes, Giemsa (G) banding See chromosome banding. Goldberg-Hogness box See TATA box. green fluorescent protein (GFP) A gene, derived from the jellyfish Aequoria victoria, that is the source of the natural bioluminescence of this species, fluo- rescing green (a 509-nm wavelength) when illumi- nated with UV light (a 395-nm wavelength). When used as a reporter gene, GFP allows a noninvasive means of visualizing gene and protein expression patterns in living organisms. guanine (G) One of four nitrogenous nucleotide bases in DNA and RNA; one of the two types of purine nucleotides in DNA and RNA. guide RNA (gRNA) In RNA editing, the nucleic acid that directs the addition or removal of nucleotides from mRNA. Also known as guide strand. guide strand See guide RN,4. gynandromorphy A condition in which the body of an organism is mosaic, appearing to contain both male and female features. hairpin structure See stem-loop. haploid number of chromosomes (n) One-half the diploid (2n) number. The number of chromosomes typically found in nuclei of gametes of diploid species. haploinsufficient A wild-type allele that is unable to support wild-type function in a heterozygous genotype. Classified as a recessive wild-type allele. Compare with haplosfficient. haplosufficient A wild-type allele that supports wild- typ e function in hetero zy gous organisms. Classified as a dominant wild-type allele. Compare with haploinsfficient. haplotype The specific array of alleles encoded by linked genes in a segment of a single chromosome. Hardy-Weinberg equilibrium The population genetic principle that in a population practicing ran- dom mating and in the absence of natural selection, mutation, migration, or random genetic drift, allele frequencies are stable at frequencies p + q: 1.0 for two alleles and are distributed into genotypes at fre- quencies p2,2pq, and q2. helicase In DNA replication, the enzyme responsible for breaking hydrogen bonds between complementary nucleotides of a DNA duplex. Unwinding of the strands occurs ahead of the advancing replication fork. helix-turn-helix (HTH) motif A DNA-binding pro- tein domain consisting of two alpha helices: one helix binds to a specific DNA sequence, and the second helix stabilizes the interaction. G LOSSARY G.7 hemizygous Referring to the genotype of males that carry a single copy of each X-linked gene. hemoglobin (Hb) A globin protein composed of four polypeptides (two o-globin and two p-globin) found in blood that transports oxygen. heritability See broad sense heritability and narrow sense heritability, heterochromatin A chromosome region containing densely compacted chromatin and few, if any, expressed genes. See constitutive heterochromatin and facultativ e hetero chro matin. Also known as hetero chro matic regio n, heteroduplex DNA A DNA duplex created during homologous recombination by combining comple- mentary strands of DNA from nonsister chromatids. Also known as heteroduplex region. heteroplasmic cell or organism A cell or organism that harbors a mixture of alleles of an organellar gene. Also known as heteroplasmy. heteroplasmy See heteroplasmic cell or organism. heterozygous advantage In evolution, the greater relative fitness of heterozygous organisms compared to homozygous organisms in a population. May result in a balanced polymorphism. Hfr cellAn abbreviation for "high frequency recom- bination," pertaining to Hfr chromosomes or to Hfr donors in bacterial conjugation. Hfr chromosome See Hfr donor. Hfr donor A donor bacterial strain containing an F factor integrated into its chromosome. Also known as Hfr chromosome. histone acetyltransferase (HAT) Chromatin- modifying enzyme that adds acetyl groups to speciflc positively charged amino acids (e.g., lysine) in the N-terminal tails of histones. histone deacetylase (HDAC) Chromatin-modifying enzyme that removes acetyl groups to specific positively charged amino acids (e.g., lysine) in the N-terminal tails of histones. histone demethylase (HDMT) Chromatin- modifyingeruzyme that removes methyl groups to specific positively charged amino acids (e.9., lysine) in the N-terminal tails of histones. histone methyltransferase (HMT) Chromatin- modifyingenzyme that adds methyl groups to specific positively charged amino acids (e.g., lysine) in the N-terminal tails of histones. histone proteins (H1, H2A,H2B, H3, H4) Five proteins encoded by a gene family that form octameric nucleosomes (H2A,H2B, H3, and H4) and adhere to DNA to condense chromatin (H1). Holliday junction A DNA structure that forms dur- ing meiotic recombination in which single strands are crossed over between nonsister chromatids of homologous chromosomes. Holliday model Proposed originally by Robin Holliday; a model intended to explain meiotic recom- bination at a molecular level. holoenzyme A fully functional multisubunit protein complex in bacteria, for example, the RNA poly- merase holoenzyme. homeobox A conserved sequence of DNA of 180 nucleotides encoding a homeodomain composed of three a-helices in a family of transcription factors found throughout eukaryotes; in metazoans some genes with homeobox genes are homeotic genes. homeodomain A 60-amino acid DNA-binding domain. G-8 GLOSSARY homeotic aene Gene that controls the developmen- tal fate of a region of the body of an organism; examples include the Hox genes in metazoans and the MADS-bozc genes in flowering plants. homeotic mutation Mutation in which an apparently normal organ or body part develops in an inappropriate location. homologous chromosomes Chromosomes that synapse (pair) during meiosis. Chromosomes with the same genes in the same order. Also known as homologous p air, homologs, homologous genes Genes descended from a com- mon ancestral gene. Also known as homologs. homologous nucleotides Nucleotides descended from a common ancestral nucleotide. homologous recombination Exchange of genetic information between homologous DNA molecules. homoplasmic cell or organism A cell or organism in which all copies (alleles) of a cytoplasmic organelle gene are the same. Also known as homoplasmy. hotspot of mutation A location within a gene or genome at which mutations occur much more often than average. housekeeping genes Genes that have essential cellular or physiological functions. Hox genes Members of the homeobox gene clusters found throughout metazoans; the genes often pattern the anterior-posterior axis and are homeotic genes. hybrid dysgenesis In Drosophila,thefailure of F1 progeny of P-cytotype males crossed with M-cytotype females to develop due to the presence of P elements. hybrid vigor The greater growth, survival, and fertility of hybrids produced by crossing highly inbred lines. hybridization (of molecular probe) In an elec- trophoresis gel or in gel blotting, the binding of a single-stranded nucleic acid probe to a single-stranded target nucleic acid by complementary base pairing. hydrogen bond Weak electrostatic attraction formed by the sharing of a positively charged hydro- gen atom by negatively charged oxygen and nitrogen atoms. Hydrogen bonds form between complemen- tary nucleotides to hold nucleic acid strands together. hypermorphic mutation A mutant whose pheno- type is similar to, but greater than, the wild-type phenotype. hypomorphic mutation See leaky mutation. identical by descent (lBD) A homozygous genotype in an organism in which both copies of the allele in an individual can be traced back to a common ancestor. illegitimate recombination Exchange of genetic information between non-homologous DNA molecules. imprinting control region (lCR) Master regulatory cis-acting DNA sequences to which trans-acting factors bind to regulate genomic imprinting. inbreeding Mating between relatives. Also known as co nsanguineous mating, inbreeding depression A reduction in vigor, survival, or reproductive fitness of offspring due to inbreeding. incomplete dominance The observation that the phenotype occurring in heterozygous organisms is intermediate between the phenotypes of homozy- gous organisms, but more similar to one homozygous phenotype than to the other. Also known as partial dominance. incomplete genetic linkage The occurrence of crossing over between linked genes. incomplete penetrance The occurrence of individual organisms that have a particular genotype or allele but not the corresponding phenotype. induced mutations Mutations generated by exposure to physical, chemical, or biological mutagens. inducer An accessory molecule that binds to a pro- tein that leads to activation of gene expression. The inducer can bind to a repressor protein and prevent its function or bind to an activator protein and stim- ulate its function. inducer-repressor complex A molecular complex consisting of a repressor protein and a bound inducer molecule. inducible operon Operon that is not expressed under one set of environmental conditions, but whose transcription is activated under an alternative environmental condition (i.e., the lac operon). induction Process by which one cell or tissue pro- motes a particular developmental fate in neighboring cells or tissues. inductive signal A molecule that acts non-cell autonomously to influence cell fate; in C, elegans vulval development, the lin-3 protein secreted from the anchor cells acts as an inductive signal to influence the fate of vulval precursor cells. informational genes Class of genes that encode pro- tein products that perform informational processes in the cell such as DNA replication, packaging of chro- mosomes, transcription, and translation. ingroup A species within a clade used to compare to other members of the clade. inhibition Process by which one cell or tissue pre- vents a particular developmental fate in neighboring cells or tissues. inhibitor An accessory molecule that converts activa- tor proteins to an inactive conformation by binding to an allosteric binding domain of the activator protein. initial committed complex In eukaryotic transcrip- tion, a partially completed multiprotein complex that is preparing to bind RNA polymerase II. initiation complex In eukaryotic translation, the complex formed by the small ribosomal subunit, mRNA, and charged IRNA -carrying methionine. initiation factor (lf 1 4 group of proteins, associated with ribosomes, that contribute to ribosome assem- bly and translation initiation. initiator IRNA The first charged tRNA associated with the ribosome. inosine (l) A modified nucleotide found occasionally in anticodons that can base-pair with uracil, cytosine, or adenine. insertional inactivation A process of mutation in which the insertion of DNA into a gene renders it nonfunctional. in situ hybridization A laboratory method for hybridizing a molecular probe to a DNA sequence or a gene on an intact chromosome. insulator sequence Cis-acting sequences that act to prevent cross-talk between regulatory elements of an adjacent gene and are located between enhancers and promoters of genes that are to be insulated from the effects of the enhancer. interactive variance (y,) In polygenic and multifac- torial inheritance, the proportion of total phenotypic variance that is due to the interactions of genetic and environmental factors. interactome The sum of all of the protein-protein interactions in an organism. interchromosomal domain Open spaces between chromosome domains in the interphase nucleus. interference (l) Measured on a zero to 1.0 scale, the measurement of the independence of crossovers. Expressed as 1.0 minus the cofficient of coincidence. internal control region (lCR) promoter consensus sequences of certain rRNA and IRNA genes that are downstream of the start of transcription (i.e., sequences that are internal to the transcriptional region of the gene). internal promoter element Promoter consensus sequences of snRNA and tRNA genes that are down- stream of the start of transcription (i.e., sequences that are internal to the transcriptional region of the gene). interphase The multiphase period of the cell cycle between cell divisions. See also G, phase, S phase, and G2 phase. interrupted mating A technique used to map bacterial genes that stops conjugation at timed inter- vals to determine which genes have transferred from the donor cell to the recipibnt cell. interspecific comparison Any comparison between different species. Compare with intraspecffic comtrtarison. interstitial deletion The loss of a portion of a chro- mosome from within one arm. intragenic recombination Crossing over within a gene. intragenic reversion A reversion produced by a second site mutation within a single gene. intraspecific comparison Any comparison between individuals of the same species. Compare with interspecific comparison. intrinsic termination In bacterial transcription, the DNA sequence-dependent mechanism for tran s cr ip ti o n ter minati o n. Inverted rep eat DNA sequences induce formation of 3'mRNA stem-loop (hairpin) structures that are followed by multiple uracils (transcribed from adenines). introgression line Lines of experimental organisms in which genome segments from two or more other lines are present due to repeated back crosses between hybrids and organisms of one parental line. intron Intervening sequences between the exons of many eukaryotic genes. Present in DNA and pre-mRNA, but spliced out during pre-mRNA processing. intron self-splicing The capacity of certain RNA transcripts to undergo self-generated splicing that does not require splicing enzymes of the splicosome complex. intron splicing The spliceosome complex-driven process that removes introns from eukaryotic pre-mRNA and ligates exons to form mature mRNA. inversion heterozygote Organisms whose homologous chromosomes have different structural organization. Most commonly, one has normal struc- ture whereas the homolog carries an inversion. inversion loop At homologous chromosome synap- sis in an inversion heterozygote, the structure that forms by the looping of one chromosome to align homologous regions. inverted repeat (lR) sequence Identical or nearly identical DNA sequences located on the same mole- cule but with opposite orientations. lS (insertion sequence) element Mobile DNA elements in bacteria that cause mutations by inactivating the expression of genes into which they insert. island model In evolutionary genetics, a model of species evolution in which new species are repro- ductively isolated from an ancestral population. isoaccepting IRNA The group of tRNAs that carry the same amino acid, but recognize synonymous codons. ISWI Imitation switch complex that functions pri- marily to control the placement of nucleosomes into an arrangement that causes a region to be transcrip- tionally silent. joint probability The likelihood of an outcome requiring the occurrence of two or more simultaneous or sequential events. karyokinesis Part of telophase, the process of nuclear division between daughter cells. karyotype A digital of analog photograph of chro- mosomes arranged by conventional chromosome numbering. kilobase (kb) A length of nucleic acid containing 1000 nucleotides. kinetochore The site of attachment of multiple pro- teins that connects a spindle fiber microtubule to the centromeric region of a chromosome. Forms during M phase of cell division. knockout library Collections of mutants in which most or all genes of a particular organism have been mutated by inactivating (or "knocking out") their expression. Kozak sequence A specific consensus sequence of eukaryotic mRNA that contains the authentic start codon (nue) sequence. lac- phenotype Bacteria that are not able to grow on a medium containing lactose as the only sugar. Compare with lac+ phenotype, lac+ phenotype Bacteria that are able to grow on a medium containing lactose as the only sugar. Compare with lac- phenotype. lacAgene A gene of the bacterial lac operon; encodes lac transacetylase. Compare with lacY gene and lacZ gene. lactose (Iac) operon An inducible operon consisting of genes (lacA, lacY,lacZ) encoding enzymes allow- ing the use of lactose as a carbon source. The operon is repressed by the lac repressor regulatory protein that binds to the lac operator sequence, and is acti- vated by the CAP-cAMP complex that binds to sequences of the CAP binding site. lacY gene A gene of the bacterial lac operon; encodes lac permease, which facilitates import of lactose into the cell. Compare with lacZ gene and lacA gene. lacZ gene A gene of the bacterial lac operon; encodes B-galactosidase, which breaks down lactose into glucose and galactose. Compare with lacY gene and lacA gene, lagging strand In DNA replication, the discontinu- ously synthesized strand whose Okazaki fragments are ligated to complete new strand synthesis. Compare with leading strand, large ribosomal subunit The larger of two subunits of the ribosome. lariat intron structure During intron splicing, the structure formed by covalent bonding of the 5' gua- nine of an intron to the branch point adenine of the intron. late genes Bacteriophage genes expressed late in the lytic cycle. Encode protein products required for packaging of phage particles and lysis of the host cell. Late promoters and late operators are the regulatory sequences responsible for late gene activation. lateral inhibition Process by which one cell or tissue prevents neighboring cells or tissues from acquiring a developmental fate similar its own. law of independent assortment (Mendel's second law) The random distribution of alleles of unlinked genes into gametes. law of segregation (Mendel's first law) The separation of alleles of a gene during gamete formation. leader region Transcribed region upstream of the major enzyme encoding genes of repressible amino acid biosynthesis operons (e.9., trpL). Region encodes a small peptide whose rate of translation reflects the concentration of the amino acid (e.g., tryptophan) in the cells and consequently regulates transcription of the operon. leader sequence See signal sequence. leading strand In DNA replication, the continuously synthesized strand. Compare with lagging strand. leaky mutation A mutant whose phenotype is simi- lar to, but less than, the wild-type phenotype.Also known as hypomorphic mutation, lethal allele See lethal mutation. lethal mutation An allele that results in the prema- ture death of the organisms that carry it. Lethality most often affects homozygous organisms. Also known as lethal allele. linkage disequilibrium The nonrandom distribu- tion into gametes of alleles of linked genes. Iinkage equilibrium The random distribution into gametes of alleles of linked genes achieved by cross- ing over between the genes. linkage group A group of genes displaying genetic linkage. linker A short, chemically synthesized oligonu- cleotide that can be ligated to DNA molecules. linker DNA DNA between nucleosomes in the 10-nm fiber structure of chromatin. locus control region (LCR) Specialized enhancer element that regulates the transcription of multiple genes, often complexes of closely related genes. lod score (Iog of the odds ratio) Based on analysis of transmission in pedigrees, the statistic used to calculate the likelihood of genetic linkage between genes. long terminal repeats (LTRs) Arrays of scores to hundreds of nucleotides that bracket the ends of retroviruses integrated into host chromosomes. loss-of-function mutation A mutant that prevents the production of the wild-type protein or renders it inactive. Most commonly a recessive mutation. lysis See lytic cycle, lysogenic cycle The Iife cycle of a bacterium infected by a temperate bacteriophage that integrates into the host chromosome and replicates along with it. GLOSSARY G-9 Iysogeny See lysogenic cycle. lytic cycle The life cycle of a bacterium infected by a bacteriophage that replicates within the host cell and lyses the host to release progeny bacteriophage. M phase The cell division phase of the cell cycle. Follows interphase. macroevolution Evolutionary processes operating at the species level and higher. MADS-box A conserved sequence of DNA of 168-180 nucleotides encoding a 56-60 amino acid DNA-binding domain in a family of transcription factors found throughout eukaryotes; in flowering plants, some MADS-box genes are homeotic genes. major gene A gene that has a substantial effect on phenotypic variation. major groove The larger of two grooves formed in the DNA sugar-phosphate backbone by the helical twist of the double helix and exposing certain base pairs. mapping function Corrective calculations used to more accurately estimate recombination frequencies between linked genes. Mapping functions differ among certain species. map unit (m.u.), centiMorgan (cM) A theoretical unit of distance between linked genes on a chromosome. maternal effect genes Genes that act in the mother to impart gene products (RNA or protein) into the egg and subsequently the embryo. For maternal effect genes, the embryonic phenotype is determined by the genotype of the mother rather than that of the embryo. maternal inheritance Transmission through the female (ovule or eggcell). Compare with paternal inheritance: transmission through the male (sperm). matrix attachment region (MAR) Portions of the chromosome scaffold to which loops of chromatin are attached. mature mRNA The fully processed product of eukaryotic transcription that moves to the cytoplasm for translation. mean (p) The average value of a group of values. median In a sample distribution, the middle most values. Also known as median value. median value See median, mediator An enhanceosome complex that forms a bridge between activator proteins bound to enhancer elements and the basal transcriptional machinery bound to the promoter. meiosis The process of cell division occurring in germ-line cells. Produces four haploid gametes or spores through two successive nuclear divisions in diploid species. meiosis I First nuclear division characterizedby homologous chromosomes separating. Compare with meiosis IL meiosis ll Second nuclear division characterized by sister chromatids separating. Compare with meiosis L Mendelian genetics Referring to genetic applications and analyses using the law of segregation and the law of independent assortment originally described through experiments and analysis by Gregor Mendel. meristem Organized groups of pluripotent cells at the growing tips of plants that both generate organs and self-maintain to ensure that a pool of stem cells is always present. G.lO GLOSSARY messenger RNA (mRNA) A form of RNA transcribed from a gene and subsequently trans- lated to produce a polypeptide or protein. metacentric chromosome A chromosome with a centrally located centromere that produces long and short arms of approximately the same length. metagenome Sequence derived from whole- genome shotgun sequencing of DNA from entire nat- ural communities consisting of a range of organisms. metaphase The stage of M pha.se during which chromosomes align in the middle of the cell. metaphase plate The cell midline along which chromosomes align during metaphase. microdeletion A small chromosome deletion detectable only by using molecular methods of analysis. microduplication A small chromosome duplication detectable only by using molecular methods of analysis. microevolution Evolutionary changes at the popula- tion level. micro RNA (miRNA) Small (2I-24 nuts) regulatory RNAs produced by Dicer and acting in a RISC complex to either repress translational or cleave target mRNA molecules. Compare with RNA interference (RNA|). microsynteny Conservation of the order of a small number of genes in the same order in related species. migration A process of evolution referring to the movement of organisms and genes between popula- tions. Also known as geneJlow. minima! initiation complex In eukaryotic tran- scription, a partially completed multiprotein complex that is preparing to bind RNA polymerase II. minor groove The smaller of two grooves formed in the sugar-phosphate backbone by the helical twist of the double helix, exposing certain base pairs. missense mutation A DNA base-pair substitution that leads to production of a polypeptide in which one amino acid substitutes for another. mitochondrion An organelle, bounded by a double membrane, encoding polypeptides that interact with nuclear gene polypeptides in oxidative phosphoryla- tion to generate ATP. In many species, mitochondria also participate in other metabolic processes and biochemical reactions, including ion homeostasis and biosynthetic pathways. mitosis The process of cell division in somatic cells that produces genetically identical daughter cells through a single nuclear division. mitosome Double-membrane-bound organelles that are evolutionarily derived from mitochondria but have lost all of the ancestral genome; proteins requiring an anaerobic environment to function are imported into them. mitotic crossover Crossing over between homologous chromosomes during mitosis. modal value See mode. mode In a sample distribution, the most commonly occurring value. Also known as modal value. modern synthesis of evolution Referring to the broad-based effort beginning in the middle of the 20th century to unite Mendelian genetics with Darwin's theory of evolution by natural selection. modifier gene A gene that modifies the effect of a major gene. modifier screen A genetic screen designed to iden- tify mutations in genes that modify, either enhance or suppress, the phenotypic effects of mutations in another gene. molecular cloning The process whereby a single DNA molecule is selectively cloned from a mixture of DNA molecules and then amplified to produce a large number of identical copies. molecular genetics The subfield of genetics that studies hereditary transmission, variation, mutation, and evolution through the analysis of nucleic acids and proteins. molecular probe (probe) A single-stranded nucleic acid or antibody protein labeled with a detectable marker that attaches to a specific target molecule, allowing target molecule detection in subsequent analysis. Single-stranded nucleic acid probes detect target nucleic acids, and antibody probes bind specific target proteins. monohybrid cross A genetic cross between organisms that are heterozygous for one gene. monophyletic group A group of organisms with a single common ancestor. monosomy The presence of a single chromosome instead of a homologous pair, resulting in a chromo- some number that is 2n - L. morphogen Substance whose presence in different concentrations directs different developmental fates. multifactorial inheritance The inheritance of traits whose phenotypic variation is the result of polygenic inheritance and environmental influences. See also multifactorial trait, multifactorial trait. Traits whose phenotypic varia- tion is the result of polygenic inheritance and envi- ronmental influences. See also multifactorial inheritance. multiple cloning site (MCS) A vector DNA sequence containing several unique restriction enzyme target sequences facilitating cloning of inserted DNA fragments. multiple gene hypothesis The hypothesis that alle- les of multiple genes contribute to the production of certain traits. multiplication rule See product rule. multipoint linkage analysis A statistical method for testing and mapping alternative orders of multiple genes linked on a chromosome. Related to lod score analysis. mutagen A chemical, physical, or biological agent capable of damaging DNA and creating a mutation. mutagenesis A procedure whereby a population of organisms is mutagenized and their progeny are propagated and examined for mutant specific pheno- types.See also genetic screen. mutation An inherited change in DNA. mutation frequency The rate at which mutations occur per gene per unit of time. Most often expressed per gene per generation. mutation-selection balance An arithmetic expression used to determine the equilibrium fre- quencies of alleles in populations as a result of allele elimination by natural selection and new allele cre- ation by mutation. narrow sense heritability (h2) The proportion of total phenotypic variance that is contributed by addi- tive genetic variance. natural selection The evolutionary process operating through differences in survival, fecundity, and relative fitness of organisms with different geno- types and phenotypes. negative assortative mating A pattern of preferen- tial mating based on differences between the mating individuals. negative contro! (of transcription) Condition where binding of a repressor protein to a regulatory DNA sequence prevents transcription of a gene or a cluster of genes. negative interference Occurring when the cofficient of coincidence is greater than 1.0, the observation of more double crossovers than expected between a pair of genes. negative supercoiling Twisting of the DNA duplex in the direction opposite to the turns of the double helix. neofunctionalization The process, following gene duplication, whereby a mutation in one of the dupli- cates provides a function not performed by the original gene. neomorphic mutation A mutant expressing a new or novel function not seen in the wild type. N-formylmethionine (fMeU tRNAfMet) A modified methionine amino acid usually used as the amino acid that initiates bacterial translation. Carried by a specialized tRNA. node An evolutionary branch point in a phylogenetic tree. non-autonomous transposable element A trans- posable genetic element lacking a transposase gene and incapable of initiating transposition. nondisjunction The failure of homolog or sister chromatid separation during cell division. Results in nuclei with the wrong number of chromosomes. nonhistone proteins Numerous nuclear proteins that are not histones associated with chromosomes. non-homologous end joining (NHEJ) An error- prone mechanism of double-stranded DNA break repair in eukaryotic genomes in which damaged nucleotides are removed and blunt ends of strands are joined. noninducible Condition in which transcription of bacterial genes or operons cannot be activated. nonparental ditype (NPD) In an ascus, the occurrence of four haploid spores that are each recombinant. nonpenetrant An organism with a genotype corre- sponding to a mutant phenotype that instead displays the wild-type phenotype. nonrecombinant vector Produced in a cloning experiment when the intended vector does not pick up a DNA insert. nonrevertible mutants Mutations caused by partial deletion of DNA nucleotides that cannot be reverted to wild type. nonsense mutation A type of point mutation pro- ducing a stop codon in mRNA. nonsister chromatid A chromatid belonging to a homologous chromosome. Nonsister chromatids of homologs are involved in crossing over. non-template strand See coding strand. normal distribution The continuous distribution of outcomes predicted by chance. Also known as G aussian distribution, northern blotting A method for transferring mRNA from an electrophoresis gel to a permanent membrane or filter. north-south (NS) resolution One possible pattern for resolving a Holliday junction to separate homolo- gous chromosomes before meiotic anaphase. nuclear mitochondria! sequence (NUMTS) Mitochondrial DNA sequences found in the nucleus as a result of recent transfer from the mitochondrial genome to the nuclear genome. nuclear plastid sequence (NUPTS) Plastid DNA sequences found in the nucleus as a result of recent transfer from the plastid genome to the nuclear genome. nucleoid The region of bacterial and archaeal cells (or mitochondria or chloroplasts) where the main chromosome resides. nucleolus (plural: nucleoli) Nuclear organelle con- taining rRNA-encoding genes. nucleomorph In a secondary endosymbiosis, the nuclear genome of the secondary endosymbiont. nucleosome An octameric protein complex com- posed of two polypeptides each of histones H2A, H2B, H3, and H4, around which DNA wraps in chromatin. nucleosome-depleted region (NDR) A 100- to 150-bp region containing few nucleosomes, which lies immediately upstream of the start of transcription. nucleotide excision repair A mechanism of DNA damage repair in which a segment of one strand con- taining damaged nucleotides is excised and replaced. null mutation A mutant that produces no func- tional product. Most commonly a recessive allele. Also known as amorphic mutation. Okazakifragment A short segment of newly synthesized DNA that is part of a lagging strand and is ligated to other Okazaki fragments to complete lagging strand synthesis. oncogene A mutated form of a proto-oncogene; frequently associated with cancer development. one gene-one enzyme hypothesis Proposed by George Beadle and Edward Tatum in 1941, the hypothesis proposing that each gene encodes a spe- cific protein product and controls a distinct function. open chromatin Chromatin in which the associa- tion of DNA with nucleosomes is relaxed in regions containing regulatory sequences, allowing access by regulatory proteins and giving genes in open chro- matin the potential to be transcriptionally active. open promoter Promoters that reside in open chro- matin, resulting in constitutive transcription. See also open promoter complex, open promoter complex At transcription initiation, the stage at which RNA polymerase is bound and a short region of DNA opens to allow transcription from the template strand. See also open promoter. operationalgenes Class of genes that encode proteins involved in cellular metabolic processes (e.g., amino acid biosynthesis, biosynthesis of cofactors, fatty acid and phospholipid biosynthesis, intermediary metabolism, energy metabolism, nucleotide biosynthesis). operator Regulatory DNA sequences to which repressor or activator proteins bind. Term used in bacterial systems. operon A set of adjacent genes that are transcribed in a polycistronic mRNA and are thus coordinately regu- lated; an operon is generally considered to include associated regulatory sequences (e.g., promoter, opera- tor, etc.). Primarily found in bacteria and archaea. ordered ascus The linear sequence in an ascus of haploid spores whose arrangement allows determina- tion of the chromatids participating in crossing over. organizer Groups of cells that possess the ability to influence the fates of cells in the surrounding tissues via non-autonomous signals. origin of migration The starting point of nucleic acid or protein migration in gel electrophoresis. origin of replication The specific sequence at which DNA replication begins. origin of transfer (oriT) The site within the fertility (F) factor sequence where transfer to the recipient cell is initiated. orthologous genes Genes in different species whose origin lies in a speciation event and that can be traced to a single gene in a common ancestor of the two species. Also known as orthologs, orthologs See orthologous genes. outgroup A species related to members of a clade but outside the clade; used to root the clade. P element A specific type of transposable genetic element prevalent in the Drosophila genome. Pvalue (probability value) In the chi square test, the likelihood that a repeat experiment will produce a result as deviant or more deviant than expected in comparison to the experimental result being tested. paired-end sequencing Sequence generated from both ends of a DNA clone; provides evidence of physical linkage of the two paired sequences. pair-rule genes In Drosophila, genes that delimit parasegments along the anterior-posterior axis; examples include even-skipped and odd-skipped, paracentric inversion A chromosome inversion in which the inverted segment does not include the region of the centromere. paralogous genes Genes whose origin lies in a gene duplication event within an extant or ancestral species. Also known as paralogs. paralogs See paralogous genes. paraphyletic group A group of organisms which includes some but not all the members descended from a common ancestor. parasegment In Drosophila, the posterior part of one segment and the anterior part of its neighbor. The stripes of gene expression of pair-rule genes cor- respond to parasegments, straddling the boundaries between segments. parental (nonrecombinant) chromosome Chromosomes in gametes produced when crossing over does not take place between linked genes. Alleles marking each gene are retained in their initial (parental) configurations. parental ditype (PD) In an ascus, the occurrence of four haploid spores that are each nonrecombinant. parental generation (P generation) The parents of F1 progeny. In controlled genetic crosses, the parents are pure-breeding. parental strand The DNA strand acting as a tem- plate to direct the synthesis of a new ("daughter") strand of DNA. partial chromosome deletion The loss of a seg- ment of a chromosome. partial deletion heterozygote An organism with one wild-type chromosome and a homolog that is missing a segment. partial diploid An exconjugant bacterium that acquires a second copy of one or more genes by conjugation with an F'donor cell. partial dominance See incomplete dominance. partial duplication The duplication of a segment of a chromosome. GLOSSARY G-l 1 part:al duplication heterozygote An organism with one wild-type chromosome and a homologous chromosome with a duplicated segment. particle gun bombardment Technique of using high pressure to fire microscopic particles coated with DNA into plant cells. The particles are propelled with enough force to penetrate the cell wall and plasma membrane. particulate inheritance Mendel's theory that genetic information is transmitted from one genera- tion to the next as discrete units or elements of heredity. Pascal's triangle A diagram listing the coefficients of a given binomial expansion in which the binomial expression is expanded n number of times. PCR primers In polymerase chain reaction, short single-stranded segments of nucleic acid that bind template DNA and serve as primers from which DNA polymerase begins strand synthesis. pedigree A family tree composed of standard symbols that depicts relationships in successive generations and often displays individual phenotypes. penetrant Expression of the phenotype corre- sponding to a particular genotype. peptide bond A typ. of covalent bond that joins amino acids in polypeptide chains. Formed between the amino end of one amino acid and the carboxyl end of the adjoining amino acid. peptide fingerprint analysis A form of chromatog- raphy in which polypeptide fragments are separated and distinctive patterns revealed. peptidyl site (P site) The site on the ribosome where amino acids are joined by a peptide bond. pericentric inversion A chromosome inversion in which the inverted segment includes the region of the centromere. permissive condition Environmental condition in which environmentally sensitive (e.9., temperature sensitive) mutants exhibit the wild-type phenotype or can survive. phenocopy A phenotype similar to a phenotype caused by mutation but that is produced instead by an environmental condition. phenotype (1) The observable physical characteristics or traits of an organism. (2) The physi- cal manifestation of a specific genotype. phenotypic ratio (3:1 ratio and 9:3:3:1 ratio) A ratio or set of relative proportions between organisms with different phenotypes-e.g., The ratio of progeny produced by a monohybrid cross (3:1) or a dihybrid cross (9:3:3:1). phenotypic variance (t/r) The total variance observed for a trait. phosphodiester bond A type of covalent bond formed between two nucleotides in a nucleic acid strain. Formed between the 5'phosphate group of one nucleotide and the 3'OH of the adjacent nucleotide. photoproduct A characteristic DNA lesion pro- duced by exposure to ultraviolet light. photoreactive repair A mechanism of DNA damage repair in bacteria that uses visible light energy to remove the damage done by ultraviolet irradiation. phylogenetic footprinting Technique whereby conserved sequences are identified by searching for similar sequences in species separated by large evolu- tionary distances. G-12 G LOSSARY phylogenetic shadowing Technique whereby con- served sequences are identified by first eliminating sequences that are not conserved in closely related species. phylogenetic tree A diagram of evolutionary relationships among organisms or genes based on morphological or molecular characteristics. phylogenomics Method for determining phyloge- netic relationships of organisms using genomic DNA sequence information. See also evolutionary genomics. physicalgap Sequence gap between scaffolds for which there is no clone to supply the sequence. plasmid One of multiple types of extrachromosomal circular DNA molecules that may be found in bacte- rial cells. plastid Organelle, bounded by a double membrane, descended from the cyanobacterial endosymbiont; specialized types of plastids include chloroplasts and chromoplasts. pleiotropy A single gene mutation that affects multiple and seemingly unconnected properties of an organism. pluripotent State of a cell when it can give rise to many but not all cell types of an organism. point mutation A DNA lesion at a defined location. Usually either a base pair substitution, or the inser- tion or deletion of one or a small number of base pairs polyacrylamide A synthetic compound mixed with buffer and used to form electrophoresis gels. polyadenylation signal sequence A hexanucleo- tide sequence of mRNA, usually AAUAAA, that iden- tifies the location of 3'pre-mRNA cleavage and polyadenylation. polycistronic mRNA In bacteria, an mRNA contain- ing the transcripts of two or more genes. polygenic inheritance A quantitative trait dependent on the contributions of multiple genes. Also known as polygenic trait. polygenic trait See polygenic inheritance. polymerase chain reaction (PCR) A laboratory method for controlled replication of a specific target sequence of DNA in successive cycles. Using two short single-stranded primers that bind to sequences on opposite sides of the target sequence, exponential replication of the target sequence occurs. polypeptide A chain of amino acids joined by peptide bonds. Formed at ribosomes during translation. polyploidy The presence of more than two com- plete sets of chromosomes in a genome. See also allop olyploidy, autopolyploidy. polyribosome In translation, the simultaneous translational activity of multiple ribosomes on a single mRNA. population A group of organisms that mate with one another to establish the next generation. population genetics The subfield of genetics that studies the genetic structure and evolution of populations. positional cloning The process by which the DNA sequence of a gene identified only by mutant pheno- type can be obtained by using genetic and physical maps. Also known as chromosome walking, positional information Process by which gene expression, or other chemical cues, establish geo- graphical addresses along the axes of a developing embryo or organ primordium. position effect variegation (PEV) The observation in Drosophila of a specific type of mutation produc- ing variegation of eye color due to the abnormal positioning of the w (white) gene for eye color. positive assortative mating A pattern of preferen- tial mating based on similarity between the mating individuals. positive control (of transcription) Condition where binding of an activator protein to a regulatory DNA sequence stimulates transcription of a gene or a clus- ter of genes. positive-negative selection The use of both nega- tive and positive selectable markers to follow the fate of introduced DNA to select for homologous recom- bination events. positive supercoiling Superhelical twisting of DNA. post-translational polypeptide processing In eukaryotes, modifications to polypeptides in the endoplasmic reticulum and Golgi apparatus after the completion of translation. postzygotic isolation mechanism Mechanisms operating after mating to reduce or prevent the possibility of producing hybrids between populations or species. precursor microRNA (pre-miRNA) The stem loop product derived from processing of pri-microRNAs. The pre-microRNA stem loop is further processed by Dicer to produce the mature single stranded microRNA from the double stranded region of the stem loop. precursor mRNA (pre-mRNA) The initial transcript of a eukaryotic gene requiring mRNA processing prior to translation. preinitiation complex In eukaryotic transcription, a large multiprotein complex containing several gen- eral transcription factors and RNA polymerase II. prezygotic isolation mechanism Mechanisms operating before mating to reduce or prevent the possibility of producing hybrids between populations or species. Pribnow box (-10 consensus sequence) A specific consensus sequence component of the bacterial promoter with a location centered at approximately -10 relative to the start of transcription. primary microRNA (pri-miRNA) The primary tran- script, with single stranded ends and a stem loop, from which pre-microRNAs are derived by process- ing. The single stranded ends of the pri-microRNA are removed, by Drosha in animals and Dicer in plants, to produce the pre-microRNA. primase The specialized RNA polymerase that synthesizes the RNA primer during DNA replication. primer annealing In PCR, the binding by complementary base pairing of a short single- stranded primer by complementary base pairing. primer extension In PCR, the synthesis of DNA by DNA polymerase beginning at the 3'end of a short single-stranded primer. primer walking Technique for sequencing long DNA molecules where new sequencing primers are synthesized based on successive DNA sequence reads. Compare with shotgun sequencing. primosome In DNA replication, a multisubunit protein complex whose central component is primase. product rule The probabiliW of an event requiring the sequential or simultaneous occurrence of two or more contributing events. The probabilities of con- tributing events are multiplied and their product is the event in question. Also known as the multiplication rule. proliferating cell nuclear antigen (PCNA) In eukaryotic DNA replication, the functional equiva, lent of the bacterial sliding clamp that adheres DNA polymerase to the template strand and drives its progression. prometaphase In M phase of the cell cycle, some- times identified as a stage between prophase and metaphase. promoter A regulatory sequence of DNA near the 5' end of a gene that acts as the binding location of RNA polymerase and directs RNA polymerase to the start of transcription. promoter mutation A mutation altering promoter sequence and function. promoter-specific element A specific promoter consensus sequence located upstream of small nuclear RNA genes. prophage The designation for bacteriophage that has integrated into the host bacterial chromosome. prophase The stage of M phase during which chromosome condensation occurs. protein A string of amino acids encoded during translation of mRNA and linked together by peptide bonds. See also polypeptide. protein sorting In eukaryotes, the process using the polypeptide leader sequence to designate the desti- nation of polypeptides. proteome Set of the proteins in a cell, tissue, or organism. proteomics The study of all the proteins, collec- tively known as the proteome, within a cell, tissue, or organism. proto-oncogene A broad category of normal genes p ro duc ing protein whose gener alize d functions promote cell proliferation. It is often mutated in carcinogenesis. pseudoautosomal region (PAR) Homologous regions on the X and Y chromosomes that synapse and cross over. pseudodominance The phenotypic expression of a recessive allele on one chromosome due to deletion of a portion of the homologous chromosome con- taining the dominant allele. pseudogene Sequences recognizable as mutated gene sequences often derived from gene duplication or retrotransposition events. Punnett square Named in honor of early 20th-century geneticist Reginald Punnett, a checker- board-like diagram that predicts the genotypes and genotype frequencies of progeny from a genetic cross. pure'breeding A group of genetically identical homozygous organisms that, when self-fertilized or intercrossed, only produce offspring that have a phenotype identical to the parents. Also known as true-breeding. pyrimidine dimer The specific type of lesion formed on DNA due to exposure to ultraviolet irradi- ation. Also known as thymine dimer. QTL locus analysis A method for characterizing the effects of quantitative trait loci on variation. QTL mapping A method for locating quantitative trait loci in a genome. quantitative genetics The subfield of genetics that studies quantitative traits. quantitative trait A trait exhibiting polygenic inheritance and displaying continuous phenotypic variation. quantitative trait locus (QTL) A gene contributing to the phenotypic variation of a quantitative trait. R (resistance) plasmid A type of bacterial plasmid conferring resistance to one or more antibiotic compounds. radial loop-scaffold model A model of chromatin structure that predicts rosettes of looped chromatin on a chromosome scaffold. random X-inactivation (Lyon hypothesis) Proposed by Mary Lyon in the mid-2Oth century, the process of randomly inactivating one copy of the X chromosome in each mammalian female nucleus early in zygotic development. reading frame The partitioning of sequential sets of mRNA trinucleotide segments (codons) that are used in translation to determine amino acid order of a polypeptide. realizator genes In Drosophila, the Hox target genes whose expression contributes to the character- istic morphology of each segment. recessive epistasis (9:3:4 ratio) A characteristic ratio of phenotypes produced by the interaction of two genes that control a trait in which alleles of one gene mask or reduce the expression of alleles of a second gene. recessive phenotype The phenotype observed in an organism that is homozygous for the recessive allele. Compare with dominant phenotype. recipient cell (F-cell) A bacterial cell that does not contain fertility factor DNA sequence and can conju- gate with a donor bacterium. reciprocal cross Paired crosses involving distinct parental phenotypes in which the sexes are switched (i.e., if one cross is d phenotype A X ? phenotype B, the reciprocal cross is d phenotype B X ? pheno- type A). reciprocal translocation (balanced, unbalanced) Exchange of chromosome segments between non- homologous chromosomes. If all genes are present, the translocation is "balancedi' but if genes are miss- ing, the translocation is "unbalancedl' recombinant (nonparental) ch romosome Chromosomes in gametes produced by crossing over between linked genes. Alleles marking each gene are rearranged on chromatids by crossing over. recombinant clone A combination of DNA mole- cules from different sources (e.9., vector and insert DNA), that are joined together using recombinant DNA technology. recombinant DNA technology The set of labora- tory techniques developed for amplifying, maintain- ing, and manipulating specific DNA sequences in vitro as well as in vivo. recombination frequency (r) The rate of occur- rence of recombination between a pair of linked genes. Expressed as the number of recombinants divided by the total number of meioses. recombination nodule Protein aggregations along the synaptonemal complex that are thought to play a role in crossing over. recombination repair A DNA repair mechanism that reestablishes normal DNA molecules by exchanging a damaged strand segment for a normal strand segment from another chromatid. reference genome sequence The DNA sequence of the individual or individuals used to construct the initial complete genome sequence. regulated transciption Condition in which gene expression is controlled at the transcriptional level in response to changing environmental conditions. regulatory mutation A mutation altering a regu- lated attribute of gene expression. relative fitness (w) In evolutionary genetics, the measurement of the reproductive fitnesses of organ- isms in a population relative to one another. The organism class with greatest fltness has a relative fitness of w-L.0. release factor (RF) Molecules that bind mRNA stop codons and contribute to translation termination. replicate cross Repeated crosses involving parents with the same genotypes and phenotypes. replication bubble A region of active bidirectional DNA replication containing replication forks on each end, an origin of replication in the middle, and lead- ing and lagging strands in each half of the bubble. replication fork In DNA replication, the site of the replisome structure, and the site of synthesis of leading strand and lagging strand DNA. replicative segregation Random segregation of organelles during cell division. replicative transposition Transposition carried out by replicating a copy of a transposable element and inserting the copy in a new genome location. replisome The large molecular machine located at the replication fork that coordinates multiple reaction steps during DNA replication. reporter gene A gene whose expression is easy to assay phenotypically. Fusion of reporter genes with heterologous sequences allows both transcriptional and translational expression patterns to be visualized. repressible operon Operon that is expressed under one set of environmental conditions, but whose tran- scription is repressed under an alternative environ- mental condition (i.e., the trp operon). repressor protein A transcription factor that binds to regulatory sequences associated with a gene and represses that gene's expression. reproductive isolation The absence of interbreed- ing between populations or species; often involves geographic, physical, or behavioral mechanisms or conditions. response to selection (R) The amount of change in the phenotype of a trait between parental and offspring generations as a result of selection on the parents. restriction endonuclease One of a large number of DNA-digesting enzymes, usually of bacterial origin, that cut DNA at specific recognition sites called restriction sequences. Each enzyme has its own particular restriction sequence and generates double- stranded cleavage of DNA at the restriction se- quence. Also known as restriction enzyme. restriction length polymorphism fragment A fragment of DNA generated by treatment with a restriction endonuclease. restriction map A map showing the numbers and relative positions of target sites for restriction enzymes of a DNA molecule. restriction sequence The specific base-pair sequence recognized by a particular restriction endonuclease. GLOSSARY G-l3 restriction-modification system System of a restriction enzyme with a specific recognition sequence and a modifyingenzyme that adds methyl groups to bases of the recognition sequence. The system protects the bacteria's own DNA from being digested by endogenous restriction enzymes, but allows restriction of invading exogenous DNA. restrictive condition Environmental condition in which environmentally sensitive (e.9., temperature sensitive) mutants exhibit the mutant phenotype. retrotransposon A transposable element that uses reverse transcriptase to transpose through an RNA intermediate. reverse genetic analysis (reverse genetics) Genetic analysis that begins with a gene sequence, which is used to identify or introduce mutant alleles and sub- sequently to identify and evaluate the resulting mu- tant phenotype. It is the complementary approach to forward genetics. reverse mutation rate (r4 The rate at which mutant alleles are reverted to wild-type alleles. Also known as reversion rate. reverse transcriptase Enzyme, derived from retroviruses or retrotransposons, that catalyzes the synthesis of a DNA strand (cDNA) from an RNA template. reverse transcription The process of DNA synthesis from an RNA template by the enzyme reverse transcriptase. reverse translation The process of using the genetic code to deduce the possible DNA sequences encod- ing a specific amino acid sequence. reversion mutation A mutation that alters a mu- tant to wild-type sequence and function. Also known as reversion. revertible mutant A point mutation caused by base-pair substitution or deletion of one or a few base pairs that can be reverted to wild type. rho-dependent termination (Rho protein) The process of bacterial transcription termination involv- ing rho protein. rho utilization site (rut site) The site of attachment of rho protein that aids in rho-protein-driven bacterial transcription termination. ribonucleic acid (RNA) A family of polynucleotides that are transcribed from DNA. RNAs are composed of nucleotides containing the sugar ribose, one or more phosphate atoms and one of four nitrogenous bases (A, G, C, and U). ribonucleotides Composed of ribose, one or more phosphate groups, and one of four nitrogenous bases, the nucleotides that make up RNA. See a\so adenine (A), uracil (U), guanine (G), and cytosine (C). ribose The S-carbon sugar molecule in ribonucleotides. ribosomal RNA (rRNA) A group of RNA molecules that compose part of the structure of ribosomes. ribosome Ribonucleoprotein particles, composed of rRNAs and numerous proteins, at which translation takes place. ribozymes Catalytically active RNAs. RNA editing The process of post-transcriptional addition or removal of nucleotide of certain mRNAs. RNA interference (RNAi) A regulatory gene-silenc- ing mechanism based on double-stranded RNA, which can target complementary sequences for inac- tivation. The machinery can be harnessed to silence gene expression in a reverse genetic approach. G-,14 G LOSSARY RNA polymerase The enzyme that catalyzes the synthesis of RNA. See also RN,4 pol, RNA pol I, RN,4 pol II, and RNA pol III. RNA polymerase I (RNA pol l) In eukaryotic transcription, the enzyme that transcribes certain rRNA genes. RNA polymerase ll (RNA pol ll) In eukaryotic tran- scription, the enzyme that transcribes protein-coding genes to produce mRNA. RNA polymerase lll (RNA pol lll) In eukaryotic tran- scription, the enzyme that transcribes tRNA genes. RNA primer In DNA replication, the short, single- stranded RNA segment synthesized by primase. The 3' end of the RNA primer is used by DNA poly- merase to begin synthesis of DNA. RNA-induced silencing complex (RISC) Complex containing Argonaute protein that binds small RNA molecules and targets complementary RNA mole- cules for degradation or translational repression. RNA-induced transcription-silencing (RITS) complex RISC-like complex that mediates small RNA-induced transcriptional gene silencing. Robertsonian translocation The fusion of two non- homologous chromosomes, often with the deletion of a small amount of nonessential genetic material. Also known as chromosomefusion. rolling circle replication A unidirectional mode of DNA replication used to replicate circular plasmid molecules in which the replicating circular molecule appears to reel off its nontemplate DNA strand, using the other as the template for replication. S phase The middle phase of interphase, during which DNA replication takes place. Sanger method See dideoxy DNA sequencing. saturation mutagenesis Mutagenesis aimed at identifying multiple mutant alleles for all loci in the genome of an experimental organism. scaffold A set of contigs that are physically linked. scanning In eukaryotic translation, the process used by the small ribosomal subunit to locate the authen- tic start codon. secondary endosymbiosis (tertiary symbiosis) Endosymbiotic event where one eukaryotic, usually photosynthetic, is an endosymbiont within another eukaryote resulting in an organism with genomes derived from at least two nuclear genomes and multiple organellar genomes. second-division segregation Patterns of haploid spores in an ascus that indicate the alleles were separated at the second meiotic division as a result of crossing over between a gene and the centromere. second-site reversion A specific type of reversion taking place at a location separate from the site altered to generate the original mutation. segment Division of the body along the anterior- posterior axis into a series of morphological similar units. segment polarity genes ln Drosophila, genes that delimit the anterior and posterior regions of individ- ual parasegments along the anterior-posterior axis; examples include wingless, engrailed, hedgehog, and gooseberry. selected marker screen An experimental method used to detect microorganisms with a specific genotype. selection coefficient (s) The value of the reduction in reproductive fitness for an organism (i.e., w: 1.0 - s). selection differential (5) The difference between the population mean value for a phenotype and the phenotype value of population members selected as parents for the next generation. selective growth medium The growth medium used in a selective marker screen. semiconservative replication The established method of DNA replication in which each strand of a parental duplex acts as a template for daughter strand synthesis, and each daughter duplex is com- posed of one parental strand and a complementary daughter strand. semisterility Reduced fertility, commonly the result of the occurrence of adjacent segregation during meiosis in b alanced transloc ation heter ozy gotes. sequence gap Gap between two contigs for which a clone is available for further sequencing that could close the gap. sex chromosome Homologous chromosomes that differ between the sexes. Designated X and Y in species in which females are XX and males XY. DesignatedZ and'W in species in which females are Z'W and males are ZZ. sex determination The genetically controlled processes that determine the sex of offspring. sex-influenced trait A gene, usually autosomal, whose expression differs between males and females of a species. Also known as sex-influenced expression. sex-limited trait A gene or trait expressed exclusively in one sex. Also known as sex-limited gene. sex-linked inheritance The inheritance of genes on the sex chromosomes. shared derived characteristics Characteristics or traits of organisms that evolve from more ancestral characteristics or traits found in ancestral organisms. Shine-Dalgarno sequence In bacterial translation, the 5'UTR mRNA consensus sequence that pairs with nucleotides near the 3' end of 165 rRNA in the small ribosomal subunit to orient the start codon on the ribosome. shotgun sequencing Method for sequencing large molecules of DNA that relies on redundant sequenc- ing of fragmented target DNA in the hope that all regions will be sequenced at least a few times. Contrast with primer walking. shuttle vector A vector that can replicate in two species and thus can be used to shuttle DNA sequences between them. sickle cell disease (SCD) A human autosomal recessive disorder resulting from homozygosity; a specific mutant allele (0t) of the B-globin gene that is part of hemoglobin protein. sigma (o) subunit Accessory protein that changes the promoter-recognition specificity of the bacterial RNA polymerase core enzyme. signal hypothesis The accepted hypothesis propos- ing that the polypeptide leader sequence identify post- translational processing and transport. signal sequence A string of amino acids at the N terminal and of certain eukaryotic polypeptides containing information directing post-translational processing and the extracellular destination of the polypeptide. Also known as leader sequence, signal-transduction pathway Pathways through which cells receive external messages at cell surface receptors and transmit the messages into the cell to initiate action or response. silencer A eukaryotic cis-acting DNA regulatory sequence to which trans-acting factors bind to repress transcription. silencer sequence Regulatory DNA sequences that can repress transcription of specific genes that may be located distantly from the sequence. Also known as silencers. silent mutation A base substitution mutation that changes one codon to a synonymous codon and does not alter the amino acid sequence of a polypeptide. simple transposon In bacterial transposition, a transposon containing multiple genes between two inverted repeats. single nucleotide polymorphism (SNp) A single base-pair difference in a specific genome location detected by comparing individual DNA sequences. single-stranded binding (SSB) protein In DNA replication, a protein that adheres to each template strand following unwinding by helicase to prevent strand reannealing before the arrival of the replication fork. sister chromatid cohesion The protein-based tem- porary attachment of sister chromatids facilitated by cohesin protein that resists the pulling forces of spin- dle fibers in metaphase. site-directed mutagenesis Introduction of specific nucleotide changes in a DNA molecule in vitro. site-specific recombination An exchange between two DNA molecules that requires specific sequences in common and that is catalyzed by an enzyme spe- cific to that recombination (e.g., integration of phage lambda into the E. coli genome). sliding clamp In bacterial DNA replication, the multisubunit protein complex that joins with DNA polymerase to hold polymerase on the template and helps drive polymerase along the template. small interfering RNA (siRNA) Single-stranded 2L- to 24-nucleotide RNA molecules derived from either endogenous or exogenous double-stranded RNA molecules that are incorporated in RISC to mediate RNAi. Endogenously produced siRNAs are most often from non-genic regions (e.g., repetitive RNA or products of an RNA-dependent RNA poly- merase). Exogenously produced siRNAs are often derived from invading nucleic acids (e.g., transposons and viruses). small nuclear RNA (snRNA) Regularory RNAs oper- ating in the nucleus. small nucleoid-associated proteins In bacterial DNA, small proteins localized to the nucleoid and associated with the main chromosome. small ribosomal subunit The smaller of two sub- units of the ribosome. solenoid structure See 30-nmfi,ber. somatic cell A body cell. All cells of a multicellular organism excepting those of the germ line. somatic gene therapy Gene therapy aimed at correcting a genetic defect in the somatic cells. Southern blotting A laboratory method devised by Edwin Southern for transferring DNA from an elec- trophoresis gel to a permanent membrane or filter. specialized transduction (specialized transducing phage) Transduction from a donor cell to a recipient cell of a few select genes located near the site of bacteriophage integration. spindle fiber microtubule (kinetochore, polar, and astral microtubule) Composed of tubulin proteins, the fibers emanating from centrosomes that attach to kinetochore regions (kinetochore), overlap to control cell shape (polar), or attach to the cell membrane to stabilize centrosomes (astral). spliceosome The multiprotein complex that carries out intron splicing. splicing mutation A mutation altering the normal splicing pattern of a pre-mRNA. spontaneous mutation Mutations occurring due to spontaneous events or changes involving nucleotides or nucleotide bases. square root method A method for estimating allele frequencies based on manipulation of the frequency of a homozygous genotype. 5R proteins Proteins rich in serine (S) and arginine (R); SR proteins are operative in intron splicing. SRY The sex-determining region of Y gene that initi- ates male sex development in mammals. stabilizing selection A pattern of natural or artificial selection that reduces population variation by removing organisms with extreme phenotypes. standard deviation (o) A statistical value that mea- sures the scatter of outcome values around the mean or average outcome value. Expressed as the square root of the sum of squared deviations of each value from the mean value. start codon Most commonly AuG, encoding methionine, the first codon translated in polypeptide synthesis. start of transcription The DNA location at which transcription begins. stem-loop Short double-stranded segments of RNA topped by a single-stranded loop containing unpaired nucleotides. Also known as a hairpin structure, sticky end Short single-stranded overhangs created by the cleavage of DNA by specific restriction endonucleases, which can potentially base-pair with complementary single-stranded sequences. stop codon One of three codons that bind a release factor instead of base-pairing with tRNA to initiate a series of events that stops translation. strand invasion During synthesis-dependent strand annealing and meiotic recombination, the entry of the 3' end of a displaced DNA into the intact sister chromatid. strand polarity (5' and 3') The orientation of a nucleic acid strand indicating its 5'phosphate and 3'hydroxyl ends. strand slippage During DNA replication, a muta- tional event leading to increased or decreased num- bers of repeating nucleotides in newly synthesized DNA and caused by slippage of DNA polymerase on the template strand or slippage of the newly synthe- sized strand on DNA polymerase. structural genomics The sequencing of whole genomes and the catalogin1t ot annotation, of sequences within a given genome. structural maintenance of chromosomes (SMC) A category of bacterial proteins localized to the nu- cleoid and associated with the main chromosome. structural motif The characteristic three dimen- sional structure of a protein, sometimes obtained from crystal structure data. Su(var) mutations Mutations that suppress position effect variegatio n in D ro s o phil a. Mutated genes produce proteins that are active in chromatin remodeling. subcloning Process by which DNA clones are further subdivided in order to clone still smaller fragments for analyses. subfunctionalization The process, following gene duplication, whereby mutations in each of the two copies can result in the two genes having comple- mentary activities such that their combined activity is the same as the activity of the gene before duplication. submetacentric chromosome A chromosome with a centromere located near the midpoint that produces long and short arms of different lengths. sugar-phosphate backbone The alternating sugar (deoxyribose or ribose) and phosphate molecule pattern of nucleic acid strands formed by the forma- tion of phosphodiester bonds linking nucleotides in the strand. sum rule The probability of an event that can result from two or more equivalent outcomes. The proba- bilities of the contributing events are added, and their sum is the probability of the event in question. Also known as the addition rule, supercoiled DNA The superhelical twisting of covalently closed circular DNA. See positive sup erco iling and negativ e sup erco iling. suppressor screen A modifier genetic screen designed to identify mutations in genes that suppress the phenotypic effects of mutations in another gene. SWI/SNF (switch/sucrose nonfermentable) A yeast chromatin-remodeling complex that modulates nucleosome positioning in an ATP-dependent manner. SWR1 (switch remodeling 1) A chromatin- remodeling complex responsible for replacing the common histone 2A protein of nucleosomes with a variant form known as H2AZ. sympatric speciation An evolutionary process in which new species form in overlapping regions. Reproductive isolation mechanisms accompanying speciation are usually behavioral or mechanical. synapsis The close approach and contact between homologous chromosomes during early prophase I in meiosis. synaptonemal complex A specialized three-layer protein complex, consisting of a central element and two lateral elements, that forms between homologous chromosomes at synapsis. syncitium A multinucleated cell in which the nuclei are not separated by cell membranes. syncytial blastoderm Stage of Drosophila embryogenesis in which the nuclei are located at the periphery of the embryo but are not separated by cell membranes. synonymous codon The groups of codons that specify the same amino acid. syntenic genes Genes located on the same chromosome. synteny The conserved order ofgenes together on a chromosome in species that share a common ancestor. synthesis-dependent strand annealing (SDSA) An error-free mechanism for repair of DNA double- strand breaks occurring after the completion of DNA replication and utilizing strand invasion to provide wild-type sequences for repair. synthetic lethality The situation where a particular double mutant results in lethality but the two respective single mutants are viable. systems biology Prediction of biological functions of genes based on correlations between different data sets. GLOSSARY G.I5 T strand The DNA strand of the T-DNA cleaved to initiate the transfer of plasmid DNA during rolling circle replication. targeted induced local lesions in genomes (TILLING) A reverse genetic approach in which a population of organisms of an inbred strain is ran- domly mutagenized throughout the genome, and this population is then screened to find mutations in a gene of interest for which the sequence is known. TATA-binding protein (TBP) A general transcription factor protein that binds the TATA box and assists in binding other transcription factors and RNA Poly- merase II to promoters. TATA box The thymine- and adenine-rich consensus sequence region found in most eukaryotic promoters. Also known as Goldberg-Hogness box. TBP-associated factors (TAF) Specific general tran- scription factors that associate with TATA-binding protein. telocentric chromosome A chromosome with a centromere located at one end, producing a long arm only. telomerase The ribonucleoprotein complex whose RNA component provides a template used to synthe- size repeating DNA segments that form chromosome telomeres. telomere Repeating DNA sequences, synthesizedby telomerase, at the ends of linear chromosomes in eu- karyotes; contain dozens to hundreds of copies of specific short DNA sequence repeats that buffer the coding sequence of the chromosome from loss dur- ing successive cycles of DNA replication. telophase The last stage of M phase, inwhich the nuclear contents are divide d (karyokinesis) and the daughter cells are divided (cytokinesis). temperate phage A bacteriophage, such as i phage, that can integrate into the bacterial host chromo- some and produce either the lytic or lysogenic life cycle. temperature-sensitive allele A mutation evident only at or above a certain temperature due to an abnormality of the protein product that affects its stability. template strand The DNA strand serving as a template for synthesis of a complementary nucleic acid strand. terminal deletion The loss of a chromosome seg- ment that includes the telomeric region. termination sequence DNA sequences that serve to stop transcription. Also known as transcription termination. termination stem loop Stem loop of an mRNA transcript that signals RNA polymerase to terminate transcription in the leader region of bacterial attenuator-controlled operons (e.g., trp opeton). test cross The cross of an organism with the domi- nant phenotype that may be hetetozygous with an organism that is homozygous for a recessive allele. Also known as test-cross analYsis. tetrad An ascus containing four haploid spores. tetrad analysis The analysis of genetic linkage by analysis of different tetrad segregation types. tetratype (TT) In an ascus, the occurrence of both types of parentals and both types of recombinants among the spores. third-base wobble The flexibility of purine- pyrimidine base pairing between the third base of a codon and the corresponding nucleotide of the anticodon. G-l6 GLOSSARY three-point test-cross analysis A test cross designed to identify genetic linkage between three genes and to provide data for determination of recombination frequency between linked genes. three-strand double crossover The occurrence of double crossover involving three of the four chromatids. threshold of genetic liability In polygenic and multifactorial inheritance, a trait with different phenotypes (i.e., affected and unaffected) that are determined by whether individual organisms are above or below a particular critical value on the phenotypic scale. Also known as threshold trait. threshold trait See threshold of genetic liability. thymine (T) One of four nitrogenous nucleotide bases in DNA; one of the two types of pyrimidine nucleotides in DNA. thymine dimer See pyrimidine dimer, tiling array DNA array that contains all sequences of the genome or a genomic interval, including introns, exons, untranslated regions (UTRs), and intergenic regions. time-of-entry mapping A method of donor gene mapping by conjugation that uses interrupted mating to determine the order and relative timing of gene transfer. Ti plasmid A large (200 kb) circular plasmid of Agrobacterium tumefaciens that harbors genes for transfer of DNA into plants cells and genes that cause uncontrolled division of plant cells; hence, the tumor-inducing (Ti) plasmid. It has been engineered for the construction of transgenic plants. topoisomerases Enzyme that relaxes DNA supercoiling by controlled strand nicking and rejoining. totipotency State of a cell when it can give rise to any and all cell Wpes of an organism. trans-acting Acting between two molecules (e.g., DNA sequences that control expression of genes interacting with a diffusible protein product). trans-acting regulatory protein Proteins that act in trans by binding to cis-acting regulatory sequences and consequently regulating nearby genes, either by activating or repressing transcription. Often referred to as transcriptionfactors, transcription The cellular process that synthesizes RNA strands from a DNA template strand. transcription factors (TFs) Proteins that bind promoters and are functional in transcription. transcription-terminating factor I (TTFI) A specific protein that binds a termination sequence to stop transcription. transcription termination See termination sequence. transcriptome Set of transcripts present in a cel[, tissue, or organism. transcriptomics The study of all the transcripts, col- lectively known as the transcriptome, within a cell, tissue, or organism. transductant The bacterium that is the product of transduction. transduction In bacterial systems, the process of transfer of DNA from a donor bacterial cell to a re- cipient cell using a bacteriophage as a vector. More generally can refer to the process by which foreign DNA is introduced into another cell via a viral vector. transfer DNA (T-DNA) The portion of the Ti plasmid that is transferred from the bacterium into the nucleus of a plant cell. transfer RNA (IRNA) A family of small RNA mole- cules that each bind a specific amino acid and convey it to the ribosome, where the anticodon sequence undertakes complementary base pairing with an mRNA codon during translation. transformant The bacterium that is the product of transformation. transformation 1) The bacterial process of gene transfer in which donated DNA fragments originat- ing in a dead donor cell, or plasmid DNA, is taken up across the cell wall and membrane of a recipient cell and recombined into the transformant genome. 2) More generally refers to the process by which ex- ogenous DNA is directly taken up by a cell resulting in a genetic alteration of the cell. 3) The conversion of animal cells to an abnormal unregulated state by an oncogenic virus or by transforming DNA. transgene A gene that has been modified in vitro by recombinant DNA technology and introduced into the genome via transformation. transgenic organism An organism harboring a transgene. transition mutation A type of DNA base-pair sub- stitution in which one purine replaces the other or one pyrimidine replaces the other. translation The process taking place at ribosomes to synthesize polypeptides. Complementary base pairing between mRNA codons and IRNA anticodons deter- mines the order of amino acids composing the polypeptide. translation repressor protein In bacteria, proteins that regulate translation by binding mRNA in the vicinity of the Shine-Dalgarno sequence and thereby prevent ribosome binding. translesion DNA synthesis Utilizing a bypass poly- merase, a mechanism for replicating DNA in the presence of damage that blocks replication by the common polymerase. translocation heterozygote An organism with chromosome translocation in which chromosome pairs consist of one normal chromosome and a homolog carrying a translocation. transmission genetics The subfield of genetics con- cerned with assessment and analysis of gene transfer from parents to offspring. Synonymous with Mendelian genetics, transposable genetic element A class of DNA sequences that can move from one chromosome location to another, either by excision and reinsertion or by replication and reinsertion of the replicated copy. transposition The process by which mobile genetic elements move from one portion of a genome to another. See also transposable genetic element. transposon tagging Technique used to identify and clone genes through insertion of a transposon into the target gene. transversion mutation A typ. of DNA base substi- tution mutation in which a purine substitutes for a pyrimidine, or vice versa. tree of life The phylogenetic tree depicting the evolutionary relationships between organisms. trihybrid cross A genetic cross between organisms that are heterozygous for three genes. trinucleotide repeat disorder A hereditary disorder caused by a mutant gene containing an increased number of repeats of a DNA trinucleotide sequence. trisomy The presence in a genome of three copies of a chromosome rather than a homologous pair of chromosomes, and resulting in a number of chromosomes that is 2n - l. trisomy rescue In a trisomic genome, the random loss of one extra chromosome to reduce the chromo- some number to the diploid. trivalent synaptic structure The specific synaptic arrangement of three homologous chromosomes in a trisomic genome. true-breeding See pure-breeding. true reversion A type of reversion that exactly reverses the original mutation. tumor suppressor gene A broad category of normal genes whose generalized functions slow, pause, or stop cell proliferation. It is often mutated in carcinogenesis. two-hybrid system A method for discovering whether two proteins interact using the GAL4 pro- tein of yeast, which is separated into a DNA-binding domain and a transcriptional activation domain. The two GAL4 domains are fused with the two proteins of interest respectively, and the resultant fusion pro- teins are assayed for their ability to activate transcrip- tion, which indicates interaction of the two proteins of interest. two-point test-cross analysis A test cross designed to identify genetic linkage between two genes and to provide data for determination of recombination frequency between linked genes. two-strand double crossover The occurrence of a double crossover involving trvo of the four chromatids. ultraviolet (UV) repair A multiprotein DNA damage repair system that corrects lesions caused by exposure to ultraviolet irradiation. uncharged tRNA A tRNA not carrying an amino acid. unequal crossover Resulting from the improper synaptic pairing of homologous chromosomes and crossing over between the mispaired chromosomes. A source of duplication and deletion of genetic material. uniparental disomy In a genome, the presence of a pair of homologous chromosomes that originate from a single parent. uniparental inheritance Condition in organellar inheritance whereby just one parental gamete- often the maternal gamete-contributes all of the cytoplasmic organelles. unordered tetrad Haploid spores in an ascus that are arranged in random order. unpaired loop At synapsis involving partial deletion or partial duplication of one chromosome of a homologous pair, the "extra" genetic material that does not have a homolog on the paired chromosome. unselected marker screen An experimental technique used to screen microbial genotypes. Commonly used following selected marker screening. unstable mutant phenotype A mutation with an unusually high frequency of reversion. upstream Referring to a gene or sequence location that is toward the 5' direction of a coding strand. upstream activator sequence (UAS) An enhancer- like sequence in yeast, located just upstream of the genes they regulate. upstream control element An upstream consensus sequence found in certain eukaryotic gene promoters. uracil (U) One of four nitrogenous nucleotide bases in RNA; one of the two types of pyrimidine nucleotides in RNA. variable expressivity Variation in the degree, magnitude, or intensity of expression of a phenotype. variance (S2) A statistical measurement of the variation of sample values around the mean value. vector A DNA fragment with attributes that will allow its amplification (origin of replication) in a bio- logical system and serves as a carrier for foreign DNA inserted into it. Vectors usually also possess genes (e.g., encoding resistance to an antibiotic) that allow selection of hosts carrying the vector. western blotting A method for transferring protein from an electrophoresis gel to a permanent mem- brane or filter. whole-genome shotgun (WGS) sequencing An approach to genome sequencing whereby DNA representing the entire genome is fragmented into smaller pieces, and a large number of fragments are chosen at random and sequenced with the aim that all genomic regions will be sequenced multiple times. Compare with clone-by-clone sequencing. whole-genome tiling array A microarray on which sequences representing the entire genome are present. X/autosome ratio (X/A ratio) The ratio of X chro- mosomes to a pair of autosomes. Used in Drosophila as the mechanism of sex determination. X-linked dominant A pattern of inheritance consis- tent with the transmission of a dominant allele of a gene on the X chromosome. Compare with X-linked recessive. X-linked inheritance The pattern of inheritance characteristic of genes located on the X chromosome. X-linked recessive A pattern of inheritance consis- tent with the transmission of a recessive allele of a GLOSSARY G.17 gene on the X chromosome. Compare with X-linked dominant. yeast artificial chromosome (YAC) Cloning vector used in yeast that utilizes an endogenous yeast origin of replication, centromere, and telomere; can accept DNA inserts in excess of 1 megabase. Y-linked inheritance The exclusively male-to-male transmission of genes on the Y chromosome. 2,,'"* The most likely recombination distance (theta [0] value) between genes as determined by lod score analysis. zone of polarizingactivity (ZPA) The posterior side of the limb bud that acts as an organizer, secreting Sonic hedgehog (Shh) protein that acts to pattern the developing limb. ZfiN system The sex chromosome inheritance system in species in which the male is homogametic (ZZ) and the female is heterogametic (ZW). zygotic genes Genes that are active only in the zygote or embryo. For zygotic genes, the genotype of the embryo determines the phenotype.