Genetics

What is DNA?
Deoxyribonucleic acid is a nuclei acid that contains the genetic information use for
development and functioning. The main role of DNA molecule is to store long term storage of
information. DNA can be compared to codes, in which it contains the instructions needed to
construct other components of cells, such as proteins and RNA molecules. The carrier of the
genetic information is called genes. Their lengths are roughly
around 1.6 mm.

DNA are made up of two long polymers called nucleotides,

and backbones that is made up of sugars and phosphate. The
two strands run in opposite direction, but they are not
parallel to each other. DNA is stored as a code by four
chemical bases which are Adenine (A), Guanine (G), Cytosine
(C), and Thymine (T). Human DNA contains about 3 billion
bases, and 99% of the human population contains the same
bases. The order and the sequence of these bases determine
the information available for building and maintaining an organism. DNA bases are paired up
with each other, A with T, C with G. Each of the bases is attach to a sugar molecule and a
phosphate molecule.

DNA Replication
DNA replication is semi-conservative and DNA replicaion only occurs at a specific step in the cell
cycle. Each strand of DNA in the double helix (spiral form that looks like a ladder) serves as a
pattern for duplicating the sequence of bases. When cells divide, each new cell needs to have
an exact copy of DNA present from the old cell. To prepare for DNA replication, a series or a
number of proteins aid are required because DNA must be single-stranded before replication
can start.

1) DNA Helicases are proteins that bind to the double stranded DNA and stimulate the
separation of the two strands.
2) DNA single-stranded binding proteins- These proteins bind to the DNA as a tetramer (a
molecule made of four monomers) which then stabilizes the single stranded structure.
Replication is a hundred time faster when these proteins are attached to the single
stranded DNA.
3) DNA Gyrase-This enzyme catalyzes (increase the rate of a chemical reaction) the
formation of negative supercoils
 4) DNA Polymerase-DNA Polymerase l (Pol l) was the first enzyme to be discovered with
polymerase activity.

How replication does occur?

DNA replication is carried out by a series of enzyme, these enzymes break up a molecule of
DNA. The unzipping occurs when hydrogen bonds between the base pairs are broken and the
two strands of the molecule unwind. DNA replication involves a host of enzymes and regulatory
molecules.

Chromosome
Eukaryotic DNA is located in the cell nucleus in the form of a number of chromosomes. The
number of chromosome varies on different species. Human have 46 chromosomes. A human
cell contains almost thousand times as many base pairs of DNA as a bacterium.

Chromosome structure
A human cell contains almost one thousand times as many
base pairs of DNA as a bacterium. The nucleus of a human cell
contains more than one meter of DNA. Even the smallest
human chromosome contains more than thirty million base
pairs of DNA. DNA and protein when they are tightly packed
they form a substance called chromatin. The chromatin
consists of DNA that is tightly spiral around proteins called
histones. DNA and histones together they make up
nucleosome. When nucleosomes are packed together they
form a thick fiber, which is shortened by a system of loops and
coils. During the most of the cell cycle, the fibers are dispersed in the nucleus so that individual
chromosomes are not visible. However during the mitosis stage, the fibers of each individual
chromosome are drawn together. They will form a tightly packed chromosome that you can see
through a light microscope in dividing cells.

What is RNA?
RNA is shorten from the word Ribonucleic acid, it is molecule that consists of a long chain of
nucleotide units. The nucleic acid molecule is similar to DNA, but it contains ribose rather than
Deoxyribo. RNA are made up of nitrogenous bases such as adenine, Uracil, guanine and
cytosine, ribose sugar and phosphate group. RNA is normally single stranded which can have a
diverse form of secondary structures. There are different types of RNA which are Messenger
RNA (mRNA), Ribosomal RNA (rRNA), and Transfer RNA (tRNA).

Messenger RNA
mRNA is produced from a gene segment of DNA which ultimately contains the information on
the primary sequence of amino acids in a protein to be synthesized. It carries the code into the
cytoplasm where protein synthesis occurs. The nucleic acid polymer is then translated into a
polymer of amino acids. In mRNA as in DNA, genetic information is fixed in the sequence of
nucleotides arranged into codons consisting of three bases. Eukaryotic transcription and
translation is closely separated, Eukaryotic mRNA must be exported from the nucleus to the
cytoplasm. Mature mRNAs are recognized by their processed modifications and then exported
through the nuclear pore.

Ribosomal RNA
rRNA, a molecular component of a ribosome, the cell's essential protein factory. Ribosomal RNA
does not make proteins because it produces polypeptides that go to make up proteins. The
ribosome is composed of two subunits, one larger than the other. Both subunits were believed
to contain both rRNA and protein.

Transfer RNA
tRNA is a small RNA molecule which transfer a specific active amino acid to a growing
polypeptide chain at the ribosomal site of protein synthesis during translation. tRNA is also
known as S-RNA (soluble or supernatant RNA), they contain about 74 – 95 Ribonucleotides.
They are made of are made up of a single stranded polynucleotide chain. There is in a 3D
L-shaped structure.

The structure of tRNA

1. The 5 terminal phosphate group.
2. The acceptor (an atom or group of atoms that accepts
electrons to form a coordinate bond during the
formation of a chemical compound) stem is a 7 base
pair (bp) stem made by the base pairing of the 5-
terminal nucleotide with the 3-terminal nucleotide
(which contains the CCA 3'-terminal group used to
attach the amino acid).
3. The CCA tail is a cytosine-cytosine-adenine sequence at
the 3' end of the tRNA molecule. This is important for
the recognition of tRNA by enzymes critical in
 translation. In prokaryotes, the CCA sequence is transcribed. In eukaryotes, the CCA
sequence is added during processing and therefore does not appear in the tRNA gene.
4. The D arm is a 4 bp stem ending in a loop that often contains dihydrouridine (adding
two hydrogen atoms to a uredines, making it a fully saturated pyrimidine ring with no
remaining double bonds).
5. The anticodon arm is a 5-bp stem where the loop contains the anticodon. It also
contains a Y that stands for a modified purine nucleotide.
6. The T arm is a 5 bp stem containing the sequence TΨC where Ψ is a pseudouridine.
7. Bases that have been tampered, especially by methylation, occur in several positions
outside the anticodon. The first anticodon base is sometimes modified to inosine or
pseudouridine. (Steps are from here http://en.wikipedia.org/wiki/Transfer_RNA)

Transcription
RNA molecules are produced by copying part of the nucleotide sequence of DNA and turn it
into a complementary sequence in RNA; the process is called transcription. During
transcription, RNA polymerase which is similar to DNA polymerase binds to the DNA and
separates the DNA strands. RNA polymerase then uses one strand of DNA as a template from
which the nucleotides are assembled into a strand of RNA. RNA polymerase does not bind to
the DNA just anywhere, the enzymes will bind at regions that is known as promoters.
Promoters are signal in DNA that indicates to the enzyme where to bind to make RNA.

RNA Editing
Many RNA molecules require a bit of editing before they are ready to go into action. Some of
the rRNA molecules that make up the ribosomes are produced from larger RNA molecules that
are cut to their final sizes. Large pieces that are removed from the RNA molecules transcribed
from many eukaryotic genes before they are functional are called introns. The introns are then
cut out of RNA molecule while they are still in the cell nucleus. Exons which are the remaining
portions are then spliced back together to form the final mRNA.

The genetic code

The genetic code consists of 64 triplets of nucleotides. These triplets are called codons.With
three exceptions, each codon converts for one of the 20 amino acids used in the synthesis of
proteins. That produces some being without a job in the code: most of the amino acids being
encoded by more than one codon. The genetic code can be expressed as either RNA codons or
DNA codons. RNA codons occur in mRNA and the codons that are actually read during the
synthesis of polypeptides (the process called translation). But each mRNA molecule acquires its
sequence of nucleotides by transcription from the corresponding gene. RNA contains four
different bases: A, U, C, and G. The genetic code is read in three letters at a time, so that each
word of the coded message is three bases long. For example how the code would be read:
UCGCACGGU would be read as UCG-CAC-GGU three letters at a time. Because there are four
different bases, there are 64 possible three base codons (4*4*4=64). Amino acids can be
specifying by more than one codon.

Translate
Translation is the first stage of protein biosynthesis (the
process in which cells build proteins). During
translation, the cell uses information from mRNA to
produce proteins. Before translation can occur; mRNA
must first be transcribed from DNA in the nucleus and
released into the cytoplasm. Then, translation begins
when an mRNA molecule in the cytoplasm attached
to a ribosome. As each codon of the mRNA molecule
moves through the ribosome, the proper amino acid is brought into the ribosome and attached
itself to the growing polypeptide chain. Each tRNA molecule has an amino acid attached to one
end and a region of three unpaired bases at the other. The three bases on the tRNA molecule,
called the anticodon, are complementary to one of the mRNA codons. In the case of the case of
the tRNA molecule for methionine, the anticodons bases are UAC, which pairs with the
methionine condon, AUG. The ribosome then forms a peptide bond between the first and
second amino acids, methionine and phenylalanine. At the same time the ribosome breaks the
bond that had held the first tRNA molecule to its amino acid and releases the tRNA molecule. In
the last step is the completing of the polypeptide. The polypeptide chain continues to grow
until the ribosome reaches a stop codon on the mRNA molecule. When it reaches the stop
codon, it releases the newly formed polypeptide, and mRNA molecule completing the process
of translation.

Differences between DNA and RNA

DNA is double stranded (double helix) and the two strands are corresponding to each other (G
with C and A with T). DNA molecules contain Deoxyribo sugars (which the number 2 carbon
bonded with Hydrogen atom.

RNA is single stranded. With the help of ribosomes, RNA makes proteins. Also there are three
types of RNA, rRNA (ribosomal RNA) mRNA (messenger RNA) and tRNA (transfer RNA) which
are balancing to each other when making a protein, however the A is not complementary with
T, but instead it is complementary with U. RNA molecules contain Ribo sugars (which the
number 2 carbon bonded with Hydroxyl group.
What are mutations?
A mutation is a permanent change in the DNA sequence of a gene. Mutations in a gene's DNA
sequence can change the amino acid sequence of the protein encoded by the gene. Gene
mutations result from changes in a single gene. The chromosomal mutations involve changes in
whole chromosomes. Mutation is not when your DNA is tampered and you turn into superman
or others. Mutation is when your DNA is tampered and you can either get cancer, or one extra
toe etc.

Gene mutation
Mutations that affect one nucleotide are called point mutations because they occur at a single
point in the DNA sequence. Some point mutations substitute one nucleotide for another thus
causing change in one of the amino acids in a protein. If a nucleotide is deleted, the base is still
read in group of three, nut the groupings are shifted for every codon that follows. Inserting an
extra nucleotide has a similar effect, changing like these are called frameshift mutations
because they shift the reading frame of the genetic message. By changing the reading frame,
frameshift mutations affect every amino acid that follows the point of the insertion or deletion.

Chromosomal mutations
This type of mutation involves changes in the number or structure of chromosomes. They can
also change the locations of genes on chromosomes and even the number of copies of some
genes. A deletion involves the loss of all or part of a chromosome. The opposite of deletion is a
duplication in which a segment of a chromosome is repeated.

Gene regulations
Only a fraction of the genes in a cell are expressed at any given time. The expressed gene is a
gene that is transcribed into RNA. At first glance, the DNA sequence of a gene is noting more
than a confusing jumble of the four letters that represent the bases in DNA. Molecular
biologists have found out that certain DNA sequences serve as promoters, binding sites for RNA
polymerase. Others serve as start and stop signals for transcript. Cells are filled with DNA-
binding proteins that attach to specific DNA sequences and help to regulate gene expression.

Gene regulation: An example

The 4288 protein encoding genes in this bacterium include a cluster of three genes that are
turned on or off together. A group of genes that operate together is known as an operon.
Because these genes must be expressed in order for the bacterium to be able to use the sugar
lactose as food, so they are called the lac operon. Lactose is a compound madeup of two simple
sugars, galactose and glucose. To use lactose for food, the bacterium must take lactose across
its cell membrane and then break the bond between glucose and galactose. These tasks are
performed by proteins coded for by the genes of the lac operon. The lacs genes are turned off
by repressors and turned on by the presence of lactose. On one side of the operon’s three
genes are two regulatory regions. In the promoter (P), RNA polymerase binds and then it begins
transcription. The other region is the operator (O). When the lac repressor binds to the O
region, RNA polymerase is prevented from binding to the promoter. Eukaryotic gene
regulations are controlled individually and have regulatory sequences that are much more
complex than those of the lac operon.

Eukaryotes need to regulate their genes for different reasons than prokaryotes. In prokaryotes, the gene
regulation allowed them to respond to their environment efficiently and economically. While eukaryotes
can respond to their environment, the main reason higher eukaryotes need to regulate their genes is
cell specialization. Whereas prokaryotes are simple, unicellular organisms, multicellular eukaryotes
consist of hundreds of different cell types, each distinguished to work for a different specialized
function. Each cell type separates by activating a different subset of genes. Most of the eukaryotic genes
are controlled

Levels of Regulation

Regulation can occur at any point in this pathway; specifically, it occurs at the levels of transcription,
RNA processing, mRNA lifetime (longevity), and translation.