A cistron is a gene.

The term cistron is used to emphasize that genes exhibit a specific behavior in a cis-
trans test; distinct positions (or loci) within a genome are cistronic.

For example, suppose a mutation at a chromosome position is responsible for a recessive trait in
a diploid organism (where chromosomes come in pairs). We say that the mutation is recessive because the
organism will exhibit the wild type phenotype (ordinary trait) unless both chromosomes of a pair have the
mutation (homozygous mutation). Similarly, suppose a mutation at another position, , is responsible for
the same recessive trait. The positions and are said to be within the same cistron when an organism
that has the mutation at on one chromosome and has the mutation at position on the paired
chromosome exhibits the recessive trait even though the organism is not homozygous for either mutation.
When instead the wild type trait is expressed, the positions are said to belong to distinct cistrons / genes.

For example, an operon is a stretch of DNA that is transcribed to create a contiguous segment of RNA,
but contains more than one cistron / gene. The operon is said to be polycistronic, whereas ordinary genes
are said to be monocistronic.

The solenoid defines the packing of DNA as a 30 nm fiber of chromatin and results from the helical
winding of at least five nucleosome strands.

In eukaryotic cells, 146 bp of DNA are wrapped approximately 1.65 times around a histone octamer (each
histone consists of 2 H2A, H2B dimers, and H3, H4 tetramer) which together are called a
nucleosome. Histone H1, which is not part of the binding histones, tightens the DNA bound to the eight
protein complex. The nucleosomes, which at this point resemble beads on a string, are further compacted
into a helical shape via the NH2 terminal protein interactions of the octameric histones, called a solenoid.

DNA packed into solenoids, unlike DNA in nucleosome form, is not transcriptionally active. With more
packing, solenoids are able to become increasingly more packed, forming chromosomes. At this point,
solenoids coil around each other to form a loop (anywhere from 20 to 80,000 base pairs), followed by a
rosette (consisting of six connected loops), then a coil, and at last, two chromatids. The end result is
the metaphase chromosome. The completely condensed chromatin has a diameter of up to 700 nm.

The average distance between the two adjacent base pairs is 0.34nm (0.34 x 10-9m
or 3.4 A). The number of base pairs in Escherichia coli is 4.6 x 106. The total
length of its DNA is 1.36 mm. Similarly 6.6 x 109bp of the two human genomes,
i.e., diploid cell will have DNA length of 2.2 metres.

The long sized DNA are accommodated in small areas (about 1 m in E. coli and 5
m nucleus in human beings) only through packing or compaction. DNA is acidic
due to presence of a large number of phosphate groups. Compaction occurs by
folding and attachment of DNA with basic proteins, non-histone in prokaryotes and
histones in eukaryotes.

DNA Packing in Prokaryotes:

DNA lies in cytoplasm. It is super coiled (coiled and recoiled) with the help of
RNAs and non-histone basic proteins like polyamines. The compacted mass of
DNA is called nucleoid or pro-chromosome.

DNA Packing in Eukaryotes:

It is carried out with the help of lysine and arginine rich basic proteins called
histones. The unit of compaction is nucleosome. There are five types of histone
proteins H1;H2A, H2B, H3 and H4. Four of them (H2A, H2B, H3 and H4) occur in
pairs to produce histone octamer, called nu body or core of nucleosome. Their
positively charged ends (due to basic amino acids) are towards the outside. They
attract negatively charged strands of DNA.
About 166 bp of DNA is wrapped over nu body for 1% turns to form nucleosome
of size 110 x 60A (116 nm). DNA connecting two adjacent nucleosomes is called
interbead or linker DNA. It bears H 1 histone protein (called plugging protein and
act as marker protein). Length of linker DNA is varied (about 145A with 70 bp).
Nucleosome and linker DNA together constitute chromatosome.

Nucleosome chain gives a beads on string appearance under electron microscope.

The beaded string is coiled to form cylindrical coil or solenoid having 6
nucleosomes per turn. Actually the nucleosomal organisation has approximately
10nm thickness, which gets further condensed and coiled to produce a solenoid of
a 30nm diameter. This solenoid structure undergoes further coiling to produce a
chromatin fibre of 30-80 nm and then a chromatid of 700 nm.

DNA nucleosome solenoid chromatin fibre chromatid chromosome

(2 nm diameter) (10 nm diameter)(30 nm diameter)(30-80 nm diameter)(700 nm

diameter) (1400 nm diameter)

Chromatin is held over a scaffold of nonhistone chromosomal or NHC proteins. At

some places chromatin is densely packed to form darkly staining heterochromatin.
At other places chromatin is loosely packed. It is called euchromatin. Euchromatin
is lightly stained. It is transcriptionally active chromatin whereas heterochromatin
is transcriptionally inactive and late replicating or heteropycnotic.
The TATA box (also called Goldberg-Hogness box) is a DNA sequence (cis-regulatory element) found
in the promoter region of genes in archaea and eukaryotes : approximately 24% of human genes contain a
TATA box within the core promoter.

Considered to be the core promoter sequence, it is the binding site of either general transcription
factors or histones (the binding of a transcription factor blocks the binding of a histone and vice versa)
and is involved in the process of transcription by RNA polymerase.

A 7- 8 base pair region of conserved homology rich in TA, preceding the transcription initiation
of the mRNA by about 1931 residues in the promoter region of eukaryotic genes:
Exceptionally, some promoter regions lack the TATA box, these are called TATA-less
promoters such as U1, U2, U4, and U5 RNA promoters. The TATA box (see Fig. H52) is
generally surrounded by GC rich sequences (proximal and distal sequence elements, PSE and
DSE). In these U promoters, PSE and DSE are still present. Transcription by RNA polymerase II
requires the association of the TATA box with a TATA binding protein (TBP) or additional TATA
associated factors (TAF). Pribnow box, TATA box, TBP, TAF,open promoter
complex, transcription factors

The TATA box has the core DNA sequence 5'-TATAAA-3' or a variant, which is usually followed by three
or more adenine bases. It is usually located 25-35 base pairs upstream of the transcription start site. The
sequence is believed to have remained consistent throughout much of the evolutionary process, possibly
originating in an ancient eukaryotic organism.

During the process of transcription, the TATA binding protein (TBP) normally binds to the TATA-box
sequence, which unwinds the DNA and bends it through 80. The AT-rich sequence of the TATA-box
facilitates easy unwinding, due to weaker base-stacking interactions between A and T bases, as compared
to between G and C. The TBP is an unusual protein in that it binds to the minor groove and binds with a
sheet.

The TATA box is usually found at the binding site of RNA polymerase II. TFIID, a transcription factor,
binds to the TATA box, followed by TFIIA binding to the upstream part of theTFIID protein. TFIIB then
binds to the downstream part of TFIID. RNA polymerase can then recognize this multi-protein complex
and bind to it, along with various other transcription factors such as TFIIF, TFIIE and TFIIH.
Transcription is then initiated, and the polymerase moves along the DNA strand,
leaving TFIID and TFIIA bound to the TATA box. These can then facilitate the binding of additional RNA
polymerase II molecules.

Symbiogenesis, or endosymbiotic theory, is an evolutionary theory that explains the origin

of eukaryotic cells from prokaryotes. It states that several key organelles of eukaryotes originated as
a symbiosis between separate single-celled organisms. According to this theory, mitochondria, plastids
(for example chloroplasts), and possibly other organelles representing formerly free-
living bacteria (prokaryotes) were taken inside another cell as an endosymbiont around 1.5 billion years
ago. Molecular and biochemical evidence suggest that mitochondria developed from proteobacteria (in
particular, Rickettsiales, the SAR11 clade, or close relatives) and chloroplasts from cyanobacteria (in
particular, nitrogen-fixing filamentous cyanobacteria)

The endosymbiosis theory postulates that

The mitochondria of eukaryotes evolved from aerobic bacteria (probably related to
the rickettsias) living within their host cell.

The chloroplasts of red algae, green algae, and plants evolved from
endosymbiotic cyanobacteria.

The Evidence

Both mitochondria and chloroplasts can arise only from preexisting

mitochondria and chloroplasts. They cannot be formed in a cell that lacks
them because nuclear genes encode only some of the proteins of which they
are made.

Both mitochondria and chloroplasts have their own genome, and it

resembles that of bacteria not that of the nuclear genome.

o Both genomes consist of a single circular molecule of DNA.

o There are no histones associated with the DNA.

Both mitochondria and chloroplasts have their own protein-synthesizing

machinery, and it more closely resembles that of bacteria than that found in
the cytoplasm of eukaryotes.

o The first amino acid of their transcripts is always fMet as it is in

bacteria (not methionine [Met] that is the first amino acid in
eukaryotic proteins).

o A number of antibiotics (e.g., streptomycin) that act by blocking

protein synthesis in bacteria also block protein synthesis within
mitochondria and chloroplasts. They do not interfere with protein
synthesis in the cytoplasm of the eukaryotes.
 o Conversely, inhibitors (e.g., diphtheria toxin) of protein synthesis by
eukaryotic ribosomes do not sensibly enough have any effect on
bacterial protein synthesis nor on protein synthesis within
mitochondria and chloroplasts.

o The antibiotic rifampicin, which inhibits the RNA polymerase of

bacteria, also inhibits the RNA polymerase within mitochondria. It has
no such effect on the RNA polymerase within the eukaryotic nucleus.

The Mitochondrial Genome

The genome of human mitochondria
contains 16,569 base pairs of DNA
organized in a closed circle. These
encode:

2 ribosomal RNA (rRNA)

molecules

22 transfer RNA (tRNA)

molecules (shown in the figure as
yellow bars; two of them labeled)

13 polypeptides

The 13 polypeptides participate in building several protein complexes

embedded in the inner mitochondrial membrane.

7 subunits that make up the mitochondrial NADH dehydrogenase

3 subunits of cytochrome c oxidase

2 subunits of ATP synthase

cytochrome b
All these gene products are used within the mitochondrion, but the
mitochondrion also needs >900 different proteins as well as some
mRNAs and tRNAs encoded by nuclear genes. The proteins
(e.g., cytochrome c and the DNA polymerases used within the
mitochondrion) are synthesized in the cytosol and then imported into the
mitochondrion.

The Chloroplast Genome

The genome of the chloroplasts found in Marchantia polymorpha (a
liverwort, one of the Bryophyta) contains 121,024 base pairs in a closed
circle. These make
up some 128 genes
which include:

duplicate
genes
encoding
each of the
four subunits
(23S, 16S,
4.5S, and 5S)
of
the ribosomal RNA (rRNA) used by the chloroplast

37 genes encoding all the transfer RNA (tRNA) molecules used

for translation within the chloroplast. Some of these are
represented in the figure by black bars (a few of which are
labeled).

4 genes encoding some of the subunits of the RNA polymerase

used for transcription within the chloroplast (3 of them shown in
blue)
 a gene encoding the large subunit of the
enzyme RUBISCO (ribulose bisphosphate carboxylase
oxygenase)

9 genes for components of photosystems I and II

6 genes encoding parts of the chloroplast ATP synthase

genes for 19 of the ~60 proteins used to construct the chloroplast

ribosome

All these gene products are used within the chloroplast, but all the
chloroplast structures also depend on proteins

encoded by nuclear genes

translated in the cytosol, and

imported into the chloroplast.

RUBISCO, for example, the enzyme that adds CO2 to ribulose

bisphosphate to start the Calvin cycle, consists of multiple copies of two
subunits:

a large one encoded in the chloroplast genome and synthesized

within the chloroplast, and

a small subunit encoded in the nuclear genome and synthesized by

ribosomes in the cytosol. The small subunit must then be imported
into the chloroplast.

The arrangement of genes shown in the figure is found not only in the
Bryophytes (mosses and liverworts) but also in
the lycopsids (e.g., Lycopodium and Selaginella). In all other plants,
however, the portion of DNA bracketed by the red arrows on the left is
inverted. The same genes are present but in inverted order. The figure is
based on the work of Ohyama, K., et al., Nature, 322:572, 7 Aug 1986;
and Linda A. Raubeson and R. K. Jansen, Science, 255:1697, 27 March
1992.

The evolution of eukaryotic chloroplasts by the endosymbiosis of a

cyanobacterium occurred in an unknown ancestor from which was
descended

the green algae and plants as described above

red algae

glaucophytes; a small group of unicellular algae.

Secondary Endosymbiosis: Eukaryotes Engulfing

Eukaryotes
The Nucleomorph

Once both heterotrophic and photosynthetic eukaryotes had evolved, the

former repeatedly engulfed the latter to exploit their autotrophic way of
life. Many animals living today engulf algae for this purpose [Link to
examples]. Usually the partners in these mutualistic relationships can be
grown separately.

However, a growing body of evidence indicates that the chloroplasts of

some algae have not been derived by engulfing cyanobacteria in a
primary endosymbiosis like those discussed above, but by
engulfingphotosynthetic eukaryotes. This is called secondary
endosymbiosis. It occurred so long ago that these endosymbionts cannot
be cultured away from their host.

In two groups, the eukaryotic nature of the endosymbiont can be seen by

its retention of a vestige of a nucleus (called its nucleomorph).
 A group of unicellular, motile algae called cryptomonads appear
to be the evolutionary outcome of a nonphotosynthetic eukaryotic
flagellate (i.e., a protozoan) engulfing a red alga by endocytosis.

Another tiny group of unicellular algae,

called chlorarachniophytes, appear to be the outcome of a
flagellated protozoan having engulfed a green alga.

In molecular biology and genetics, splicing is a modification of the nascent pre-

messenger RNA (pre-mRNA) transcript in which introns are removed
and exons are joined. For nuclear-encoded genes, splicing takes place within the
nucleus after or concurrently with transcription. Splicing is needed for the
typical eukaryotic messenger RNA (mRNA) before it can be used to produce a
correct protein through translation. For many eukaryotic introns, splicing is done in
a series of reactions which are catalyzed by the spliceosome, a complex of small
nuclear ribonucleoproteins (snRNPs), but there are also self-splicing introns.

Splicing pathways
Several methods of RNA splicing occur in nature; the type of splicing depends on the structure of the
spliced intron and the catalysts required for splicing to occur.

Introns

The word intron is derived from the term intragenic region, that is, a region inside a gene. The term intron
refers to both the DNA sequence within a gene and the corresponding sequence in the unprocessed RNA
transcript. As part of the RNA processing pathway, introns are removed by RNA splicing either shortly
after or concurrent with transcription.[1]Introns are found in the genes of most organisms and many
viruses. They can be located in a wide range of genes, including those that generate proteins, ribosomal
RNA (rRNA), and transfer RNA (tRNA).[2]

Spliceosomal introns often reside within the sequence of eukaryotic protein-coding genes. Within the
intron, a donor site (5' end of the intron), a branch site (near the 3' end of the intron) and an acceptor site
(3' end of the intron) are required for splicing. The splice donor site includes an almost invariant sequence
GU at the 5' end of the intron, within a larger, less highly conserved region. The splice acceptor site at the
3' end of the intron terminates the intron with an almost invariant AG sequence. Upstream (5'-ward) from
the AG there is a region high in pyrimidines (C and U), or polypyrimidine tract. Upstream from the
polypyrimidine tract is the branchpoint, which includes an adenine nucleotide. [3][4]The consensus sequence
for an intron (in IUPAC nucleic acid notation) is: A-G-[cut]-G-U-R-A-G-U (donor site) ... intron sequence
... Y-U-R-A-C (branch sequence 20-50 nucleotides upstream of acceptor site) ... Y-rich-N-C-A-G-[cut]-G
(acceptor site).[5] However, it is noted that the specific sequence of intronic splicing elements and the
number of nucleotides between the branchpoint and the nearest 3 acceptor site affect splice site selection.
[6][7]
Also, point mutations in the underlying DNA or errors during transcription can activate a cryptic
splice site in part of the transcript that usually is not spliced. This results in a mature messenger RNA with
a missing section of an exon. In this way, a point mutation, which usually only affects a single amino
acid, can manifest as a deletion in the final protein.

Formation and activity

Splicing is catalyzed by the spliceosome, a large RNA-protein complex composed of five small nuclear
ribonucleoproteins (snRNPs, pronounced 'snurps'). Assembly and activity of the spliceosome occurs
during transcription of the pre-mRNA. The RNA components of snRNPs interact with the intron and are
involved in catalysis. Two types of spliceosomes have been identified (major and minor) which contain
different snRNPs.

The major spliceosome splices introns containing GU at the 5' splice site and AG at the 3' splice
site. It is composed of the U1, U2, U4, U5, and U6 snRNPs and is active in the nucleus. In addition, a
number of proteins including U2 small nuclear RNA auxiliary factor 1 (U2AF35), U2AF2 (U2AF65)
[8]
and SF1 are required for the assembly of the spliceosome. [4][9] The spliceosome forms different
complexes during the splicing process:[10]

Complex E

The U1 snRNP binds to the GU sequence at the 5' splice site of an intron;

Splicing factor 1 binds to the intron branch point sequence;

U2AF1 binds at the 3' splice site of the intron;

U2AF2 binds to the polypyrimidine tract;[11]

Complex A (pre-spliceosome)

The U2 snRNP displaces SF1 and binds to the branch point sequence and ATP is
hydrolyzed;

Complex B (pre-catalytic spliceosome)

The U5/U4/U6 snRNP trimer binds, and the U5 snRNP binds exons at the 5' site, with U6
binding to U2;
 Complex B*

The U1 snRNP is released, U5 shifts from exon to intron, and the U6 binds at the 5' splice
site;

Complex C (catalytic spliceosome)

U4 is released, U6/U2 catalyzes transesterification, making the 5'-end of the intron ligate
to the A on intron and form a lariat, U5 binds exon at 3' splice site, and the 5' site is
cleaved, resulting in the formation of the lariat;

Complex C* (post-spliceosomal complex)

U2/U5/U6 remain bound to the lariat, and the 3' site is cleaved and exons are ligated
using ATP hydrolysis. The spliced RNA is released, the lariat is released and degraded,
[12]
and the snRNPs are recycled.
This type of splicing is termed canonical splicing or termed the lariat pathway, which accounts
for more than 99% of splicing. By contrast, when the intronic flanking sequences do not follow
the GU-AG rule, noncanonical splicing is said to occur (see "minor spliceosome" below). [13]

The minor spliceosome is very similar to the major spliceosome, but instead it splices out
rare introns with different splice site sequences. While the minor and major spliceosomes
contain the same U5 snRNP, the minor spliceosome has different but functionally analogous
snRNPs for U1, U2, U4, and U6, which are respectively called U11,U12, U4atac, and U6atac.
[14]
Unlike the major spliceosome, it is found outside the nucleus, but very close to the nuclear
membrane.[15]

Trans-splicing is a form of splicing that joins two exons that are not within the same RNA
transcript.[16]

Self-splicing[edit]
Self-splicing occurs for rare introns that form a ribozyme, performing the functions of the
spliceosome by RNA alone. There are three kinds of self-splicing introns, Group I,Group
II and Group III. Group I and II introns perform splicing similar to the spliceosome without
requiring any protein. This similarity suggests that Group I and II introns may be evolutionarily
related to the spliceosome. Self-splicing may also be very ancient, and may have existed in
an RNA world present before protein.

Two transesterifications characterize the mechanism in which group I introns are spliced:

1. 3'OH of a free guanine nucleoside (or one located in the intron) or a nucleotide cofactor
(GMP, GDP, GTP) attacks phosphate at the 5' splice site.
 2. 3'OH of the 5' exon becomes a nucleophile and the second transesterification results in
the joining of the two exons.

The mechanism in which group II introns are spliced (two transesterification reaction like group I
introns) is as follows:

1. The 2'OH of a specific adenosine in the intron attacks the 5' splice site, thereby forming
the lariat

2. The 3'OH of the 5' exon triggers the second transesterification at the 3' splice site,
thereby joining the exons together.

tRNA splicing[edit]
tRNA (also tRNA-like) splicing is another rare form of splicing that usually occurs in tRNA. The
splicing reaction involves a different biochemistry than the spliceosomal and self-splicing
pathways.

In the yeast Saccharomyces cerevisiae, a yeast tRNA splicing endonuclease heterotetramer,

composed of TSEN54, TSEN2, TSEN34, and TSEN15, cleaves pre-tRNA at two sites in the
acceptor loop to form a 5'-half tRNA, terminating at a 2',3'-cyclic phosphodiester group, and a 3'-
half tRNA, terminating at a 5'-hydroxyl group, along with a discarded intron. [17] Yeast tRNA
kinase then phosphorylates the 5'-hydroxyl group using adenosine triphosphate. Yeast tRNA
cyclic phosphodiesterase cleaves the cyclic phosphodiester group to form a 2'-phosphorylated 3'
end. Yeast tRNA ligase adds an adenosine monophosphate group to the 5' end of the 3'-half and
joins the two halves together.[18] NAD-dependent 2'-phosphotransferase then removes the 2'-
phosphate group.[19][20]

Evolution[edit]
Splicing occurs in all the kingdoms or domains of life, however, the extent and types of splicing
can be very different between the major divisions. Eukaryotes splice many protein-
coding messenger RNAs and some non-coding RNAs. Prokaryotes, on the other hand, splice
rarely and mostly non-coding RNAs. Another important difference between these two groups of
organisms is that prokaryotes completely lack the spliceosomal pathway.

Because spliceosomal introns are not conserved in all species, there is debate concerning when
spliceosomal splicing evolved. Two models have been proposed: the intron late and intron early
models (see intron evolution).

Biochemical mechanism[edit]
Diagram illustrating the two-step biochemistry of splicing

Spliceosomal splicing and self-splicing involve a two-step biochemical process.Both steps

involvetransesterification reactions that occur between RNA nucleotides. tRNA splicing, however,
is an exception and does not occur by transesterification. [21]

Spliceosomal and self-splicing transesterification reactions occur via two sequential

transesterification reactions. First, the 2'OH of a specific branchpoint nucleotide within the intron,
defined during spliceosome assembly, performs a nucleophilic attack on the first nucleotide of the
intron at the 5' splice site, forming thelariat intermediate. Second, the 3'OH of the released 5'
exon then performs a nucleophilic attack at the last nucleotide of the intron at the 3' splice site,
thus joining the exons and releasing the intron lariat.[22]

Alternative splicing[edit]
Main article: Alternative splicing

In many cases, the splicing process can create a range of unique proteins by varying the exon
composition of the same mRNA. This phenomenon is then called alternative splicing. Alternative
splicing can occur in many ways. Exons can be extended or skipped, or introns can be retained. It
is estimated that 95% of transcripts from multiexon genes undergo alternative splicing, some
instances of which occur in a tissue-specific manner and/or under specific cellular conditions.
[23]
Development of high throughput mRNA sequencing technology can help quantify the
expression levels of alternatively spliced isoforms. Differential expression levels across tissues
and cell lineages allowed computational approaches to be developed to predict the functions of
these isoforms.[24][25] Given this complexity, alternative splicing of pre-mRNA transcripts is
regulated by a system of trans-acting proteins (activators and repressors) that bind to cis-acting
sites or "elements" (enhancers and silencers) on the pre-mRNA transcript itself. These proteins
and their respective binding elements promote or reduce the usage of a particular splice site.
However, adding to the complexity of alternative splicing, it is noted that the effects of regulatory
factors are many times position-dependent. For example, a splicing factor that serves as a splicing
activator when bound to an intronic enhancer element may serve as a repressor when bound to its
splicing element in the context of an exon, and vice versa. [26] In addition to the position-dependent
effects of enhancer and silencer elements, the location of the branchpoint (i.e., distance upstream
of the nearest 3 acceptor site) also affects splicing. [6] The secondary structure of the pre-mRNA
transcript also plays a role in regulating splicing, such as by bringing together splicing elements
or by masking a sequence that would otherwise serve as a binding element for a splicing factor. [27]
[28]

Experimental manipulation of
splicing[edit]
 Splicing events can be experimentally altered[29][30] by binding steric-blocking antisense oligos such
as Morpholinos or Peptide nucleic acids to snRNP binding sites, to the branchpoint nucleotide that
closes the lariat,[31] or to splice-regulatory element binding sites.[32]

Splicing errors[edit]
It has been suggested that one third of all disease-causing mutations impact on splicing.
[26]
Common errors include:

Mutation of a splice site resulting in loss of function of that site. Results in exposure of a
premature stop codon, loss of an exon, or inclusion of an intron.

Mutation of a splice site reducing specificity. May result in variation in the splice location,
causing insertion or deletion of amino acids, or most likely, a disruption of the reading
frame.

Displacement of a splice site, leading to inclusion or exclusion of more RNA than expected,
resulting in longer or shorter exons.

Although many splicing errors are safeguarded by a cellular quality control mechanism
termed nonsense-mediated mRNA decay (NMD),[33] a number of splicing-related diseases also
exist, as suggested above.[34]

Protein splicing[edit]
Main article: Protein splicing

In addition to RNA, proteins can undergo splicing. Although the biomolecular mechanisms are
different, the principle is the same: parts of the protein, called inteins instead of introns, are
removed. The remaining parts, called exteins instead of exons, are fused together. Protein splicing
has been observed in a wide range of organisms, including bacteria, archaea, plants, yeast and
humans.[35]

The Pribnow box (also known as the Pribnow-Schaller box) is the sequence TATAAT of
six nucleotides (thymine-adenine-thymine-etc.) that is an essential part of a promoter site
on DNA for transcription to occur in bacteria. It is an idealized or consensus sequencethat is, it shows
the most frequently occurring base at each position in a large number of promoters analyzed; individual
promoters often vary from the consensus at one or more positions. It is also commonly called the -10
sequence, because it is centered roughly 10 base pairs upstream from the site of initiation of transcription.
The Pribnow box has a function similar to the TATA box that occurs in promoters
in eukaryotes and archaea: it is recognized and bound by a subunit of RNA polymerase during initiation
of transcription. This region of the DNA is also the first place where base pairs separate during
prokaryotic transcription to allow access to the template strand. The AT-richness is important to allow
this separation, since adenine and thymine are easier to break apart (not due to the hydrogen bond
count[3]).

The Shine-Dalgarno (SD) sequence is a ribosomal binding site in prokaryotic messenger RNA,
generally located around 8 bases upstream of the start codon AUG. The RNA sequence helps recruit
the ribosome to the mRNA to initiate protein synthesis by aligning the ribosome with the start codon.

The Shine-Dalgarno sequence exists both in bacteria and archaea. It is also present in
some chloroplast and mitochondrial transcripts. The six-base consensus sequence is AGGAGG;
in Escherichia coli, for example, the sequence is AGGAGGU, while subsequence GAGG dominates in E.
coli virus T4 early genes.[1]

The Shine-Dalgarno sequence was proposed by Australian scientists John Shine (b. 1946) and Lynn
Dalgarno

Extranuclear inheritance or cytoplasmic inheritance is the transmission of genes that occur outside
the nucleus. It is found in most eukaryotes and is commonly known to occur in
cytoplasmic organelles such as mitochondria and chloroplasts or from cellular parasites
like virusesor bacteria.[1][2][3]

Organelles[edit]
Mitochondria are organelles which function to transform energy as a result of cellular respiration.
Chloroplasts are organelles which function to produce sugars via photosynthesis in plants and algae.
The genes located in mitochondria and chloroplasts are very important for proper cellular function, yet
the genomes replicate independently of the DNA located in the nucleus, which is typically arranged in
chromosomes that only replicate one time preceding cellular division. The extranuclear genomes of
mitochondria and chloroplasts however replicate independently of cell division. They replicate in
response to a cell's increasing energy needs which adjust during that cell's lifespan. Since they replicate
independently, genomic recombination of these genomes is rarely found in offspring contrary to nuclear
genomes, in which recombination is common. Mitochondrial disease are received from the mother, sperm
does not contribute for it(but a sperm contains a mitochondrion for its energy production).

Parasites[edit]
Extranuclear transmission of viral genomes and symbiotic bacteria is also possible. An example of viral
genome transmission is perinatal transmission. This occurs from mother to fetus during the perinatal
period, which begins before birth and ends about 1 month after birth. During this time viral material may
be passed from mother to child in the bloodstream or breastmilk. This is of particular concern with
mothers carrying HIV or Hepatitis C viruses.[2][3] Examples of cytoplasmic [symbiotic] bacteria have also
been found to be inherited in organisms such as insects and protists. [4]

Types[
Three general types of extranuclear inheritance exist.

Vegetative segregation results from random replication and partitioning of cytoplasmic

organelles. It occurs with chloroplasts and mitochondria during mitotic cell divisions and results in
daughter cells that contain a random sample of the parent cell's organelles. An example of vegetative
segregation is with mitochondria of asexually replicating yeast cells. [5]

Uniparental inheritance occurs in extranuclear genes when only one parent contributes
organellar DNA to the offspring. A classic example of uniparental gene transmission is the maternal
inheritance of human mitochondria. The mother's mitochondria are transmitted to the offspring
at fertilization via the egg. The father's mitochondrial genes are not transmitted to the offspring via
the sperm. Very rare cases which require further investigation have been reported of paternal
mitochondrial inheritance in humans, in which the father's mitochondrial genome is found in
offspring.[6] Chloroplast genes can also inherit uniparentally during sexual reproduction. They are
historically thought to inherit maternally, but paternal inheritance in many species is increasingly
being identified. The mechanisms of uniparental inheritance from species to species differ greatly and
are quite complicated. For instance, chloroplasts have been found to exhibit maternal, paternal and
biparental modes even within the same species.[7][8]

Biparental inheritance occurs in extranuclear genes when both parents contribute organellar
DNA to the offspring. It may be less common than uniparental extranuclear inheritance, and usually
occurs in a permissible species only a fraction of the time. An example of biparental mitochondrial
 inheritance is in the yeast Saccharomyces cerevisiae. When two haploid cells of opposite mating type
fuse they can both contribute mitochondria to the resulting diploid offspring.[1][5

Okazaki fragments are short, newly synthesized DNA fragments that are formed on the lagging
template strand during DNA replication. They are complementary to the lagging template strand,
together forming short double-stranded DNA sections. Okazaki fragments are between 1000 and
2000 nucleotides long in Escherichia coli and are approximately 150 nucleotides long
in eukaryotes. They are separated by ~10-nucleotide RNA primers and are unligated until RNA
primers are removed, followed by enzyme ligase connecting (ligating) the two Okazaki fragments
into one continuous newly synthesized complementary strand.

On the leading strand DNA replication proceeds continuously along the DNA molecule as the
parent double-stranded DNA is unwound, but on the lagging strand the new DNA is made in
installments, which are later joined together by a DNA ligase enzyme. This is because the
enzymes that synthesise the new DNA can only work in one direction along the parent DNA
molecule. On the leading strand this route is continuous, but on the lagging strand it is
discontinuous

A P element is a transposon that is present specifically in the fruit fly Drosophila

melanogaster and is used widely for mutagenesis and the creation of genetically modified flies
used for genetic research. The P element gives rise to a phenotype known as hybrid dysgenesis.

P elements were discovered in the 1970s when laboratory strains used since 1905 were compared
to wild type flies (i.e. found in nature). It seemed that these P elements had swept through all wild
type populations of D. melanogaster subsequent to the isolation of the laboratory strains, which
did not contain P elements.

The P element encodes for the protein P transposase and is flanked by terminal inverted repeats
which are important for its mobility. Unlike laboratory strain females, wild type females are
thought to express an inhibitor to P transposase function. This inhibitor reduces the disruption to
the genome caused by the P elements, allowing fertile progeny. Evidence for this comes from
crosses of laboratory females (which lack P transposase inhibitor) with wild type males (which
have P elements). In the absence of the inhibitor, the P elements can proliferate throughout the
genome, disrupting many genes and killing progeny

Chargaff's rules states that DNA from any cell of all organisms should have a 1:1 ratio (base Pair Rule)
of pyrimidine and purine bases and, more specifically, that the amount of guanine is equal to cytosine and
the amount of adenine is equal to thymine. This pattern is found in both strands of the DNA. They were
discovered by Austrian chemist Erwin Chargaff.

Definitions[edit]
First parity rule[edit]
The first rule holds that a double-stranded DNA molecule globally has percentage base pair equality: %A
= %T and %G = %C. The rigorous validation of the rule constitutes the basis of Watson-Crick pairs in the
DNA double helix.

Second parity rule[edit]

The second rule holds that both %A ~ %T and %G ~ %C are valid for each of the two DNA strands.
[3]
This describes only a global feature of the base composition in a single DNA strand. [4]
Retroposons are repetitive DNA fragments which are inserted into chromosomes after they had
been reverse transcribed from any RNA molecule. In contrast retrotransposons, never encode reverse
transcriptase (RT). Therefore, they are non-autonomous elements with regard to transposition activity
(as opposed to transposons).
Retroposition accounts for approximately 10,000 gene-duplication events in the human genome, of which
approximately 2-10% are likely to be functional. [2]Such genes are called retrogenes and represent a certain
type of retroposon. A classical event is the retroposition of a spliced pre-mRNA molecule of the c-src
gene into the proviral ancestor of the Rous Sarcoma Virus (RSV). The retroposed c-src pre-mRNA still
contained a single intron and within RSV is now referred to as v-src gene.
Non-Long terminal repeat (LTR) retrotransposons such as the human L1 elements are sometimes falsely
referred to as retroposons.

1. A nucleosome is a basic unit of DNA packaging in eukaryotes, consisting of a segment of DNA

wound in sequence around eight histone protein cores. This structure is often compared to thread
wrapped around a spool.

2. Nucleosomes form the fundamental repeating units of eukaryotic chromatin,[4] which is used to
pack the large eukaryotic genomes into the nucleus while still ensuring appropriate access to it (in
mammalian cells approximately 2 m of linear DNA have to be packed into a nucleus of roughly
10 m diameter). Nucleosomes are folded through a series of successively higher order structures
to eventually form a chromosome; this both compacts DNA and creates an added layer of
regulatory control, which ensures correct gene expression. Nucleosomes are thought to
carry epigenetically inherited information in the form of covalent modifications of their
core histones. Nucleosomes were observed as particles in the electron microscope by Don and
Ada Olins [5] and their existence and structure (as histone octamers surrounded by approximately
200 base pairs of DNA) were proposed by Roger Kornberg.[6][7] The role of the nucleosome as a
general gene repressor was demonstrated by Lorch et al. in vitro [8] and by Han and Grunstein in
vivo.