ORGANIZATION OF MAMMALIAN GENOME-
Genome:
GENOME was introduced in 1920 by Hans Winkler,
professor of botany at the university of Hamburg Germany. Genome is refers to
the DNA (some time RNA) molecules that carry the genetic information in an
organism.
§ So genome is the store house of
biological information.
§ It includes – chromosomes in
nucleous and the DNA in mitochondria, chloroplasts
Genomics
: study of
the structure evolution , mapping and function of the genome is called
genomics.
They are
divided into following parts-
I.
Functional genomics: It is applied to represent the gene expression and
relationship of genes with gene production.
II.
Structural genomics: It is refer to the structural design and complex protein structure.
III.
Comparative genomics: It is refer to compare genome sequence in
different species to obtained better understanding of their similarities.
IV.
Epigenomics: Is refer
to understand how genetic changes can occur without altering the DNA sequences.
NOTE: DNA, the repository of genetic information, is present not
only in chromosomes in the nucleus of eukaryotic organisms, but also in
mitochondria and the chloroplasts of plants.
Metagenomics: Analyse the function and
structure of complete nucleotide sequences from multiple organism in a bulk
sample.
Pharmacogenomics: It is refer to the study about
how an individual’s DNA affects the way that person respond to specific drugs.
Goal of this genomics are providing more effective treatments to patients.
Organization of mammalian genome:-
·
DNA
getting packaged in a hierarchical manner to form chromatin.
- It
compressed by specialized proteins that aid in folding the DNA in a specific
manner (to avoid formation of complicated tangle.)
· Proteins involved in packaging of
DNA are-
1. Histone proteins: These proteins are highly
conserved, small, basic proteins which are rich in lysine and arginine.
|
Histone
type |
Molecular
weight |
No. of
amino acid |
Approx. content of basic amino
acids |
|
|
|
Lysine |
Arginine |
|
|||
|
H1 |
17000-18000 |
200-265 |
27% |
2 % |
|
|
H2A |
13900 |
129-155 |
11% |
9 % |
|
|
H2B |
13800 |
121-148 |
16% |
6 % |
|
|
H3 |
15300 |
136 |
10% |
15 % |
|
|
H4 |
11300 |
102 |
11% |
4% |
|
2. Non- histone proteins/ High
mobility group (HMG) proteins:- The HMG proteins are heterogeneous protein that include in DNA polymerase
regulator proteins etc.
They are
generally referred to as acidic proteins to distinguish them from basic
histones.
|
Non –
histone protein type |
Number
of amino acid |
Chemical
properties |
Location
in chromatin |
|
Ubiquitin |
74 |
Carboxyl
end they can bind to the amino terminal of lysine and histone H2A |
U- H2
Nucleosome core |
|
HMG-17 |
89 |
Soluble
in 10% Tri Chloro Acetic acid |
Linker
DNA |
|
HMG-14 |
100 |
Soluble
in 10 %TCA |
Linker DNA |
|
HMG-1 |
270 |
Soluble
in 2% TCA |
Linker
DNA |
|
HMG-2 |
270 |
Soluble in 2 % TCA |
Linker DNA |
Chromatin -The combination of histone proteins + non- histone
proteins + DNA , complex are called as chromatin.
OR
On chromosomes, the DNA is
bound up with proteins called histones to form chromatin.
This federation takes part
in epigenetics and gene regulation.
Genes are switched on and off during development and cell
activity, and this regulation is the basis of most of the activity which takes
place in cells
v DNA and histones are organized to
form a nucleosome which is the fundamental
subunit of chromatin.
v Through the electron microscope
study the chromatin show the appearance of chromatin as a series of beads on a
string.
Beads =
nucleosome core particles, string = DNA
Assemble
of nucleosome:
·
Assemble
the histones = H3 and H4 first bind to each other and histones H2A and H2B bind
to each other.
·
Two H3-H4
dimers combines to form tetramers
·
Further
binds to two dimers of H2A to form octamer core.
·
DNA is
then wound around this core.
DNA-
· DNA (deoxyribonucleic acid) is
the molecule that contains the genetic code of organisms. This includes animals, plants, protists, archaea and bacteria. It is made up of two polynucleotide chains and coil around each other to form double
helix.
·
The polymer carries genetic instructions for the development, functioning, growth
and reproduction of all known organisms and many viruses.
·
DNA and ribonucleic acid (RNA) are nucleic acids.
· There are four essential macromolecules
- proteins, lipids ,complex carbohydrates (polysaccharides), and nucleic
acids which are involve in forms of life.
·
The two DNA strands are known as
polynucleotides as they are composed of simple monomeric units called nucleotides.
·
Each nucleotide is composed with nitrogen
containing nucleobases (cytosine [C], guanine [G], adenine [A] or thymine [T]), a sugar called deoxyribose, and a phosphate group.
·
The nucleotides are joined to one another in a
chain by covalent bonds (known as the phosphodiester linkage).
Types of DNA
There are majorly three types of DNA. these include
–
·
A-DNA -The A-DNA is a right-handed double helix same as the B-DNA form
·
B-DNA – The B-DNA is a right-handed helix and is the most common DNA
conformation
·
Z-DNA – Unlike others, the Z-DNA is left-handed DNA
STRUCTURE OF DNA
DNA has a double helix shape, which
is like a ladder twisted (step) into a spiral. Each step of the
ladder is a pair of nucleotides.
Nucleotides
A nucleotide is a molecule made up of:
·
Deoxyribose, it’s a kind of sugar with 5 carbon atoms,
·
Phosphate group made of phosphorus and oxygen, and
·
nitrogenous base
DNA is made of four types of
nucleotide:
·
Adenine (A)
·
Thymine (T)
·
Cytosine (C)
·
Guanine (G)
The 'rungs' of the DNA ladder
made of two bases, one base coming from each leg. The bases connect in the
middle: 'A' only pairs with 'T', and 'C' only pairs
with 'G'. The bases are helix together by hydrogen bonds.
Adenine (A) and thymine (T)
can pair up because they make two hydrogen
bonds, and cytosine (C) and guanine (G) pair
up to make three hydrogen bonds. Although the bases are always in fixed pairs, the pairs
can come in any order (A-T or T-A; similarly, C-G or G-C).
This way, DNA can write 'codes' out of the
'letters' that are the bases. These codes contain the message that tells the
cell what to do.
Functions of DNA
·
DNA can be determined as a genetic material responsible
for carrying all the hereditary information (genetic information).
· All
organisms have several genes in their DNA, which means multiple types of
proteins can be formulated.
·
DNA is not only responsible for storing genetic
information, but they perform several other functions as well. These include-
·
Replication process - (Double-stranded
DNA molecule is copied to produce two identical DNA molecules.
·
Cellular metabolism - (Deoxyribonucleic
acid (DNA) is maintained)
·
DNA fingerprinting - (identity of a
person based on the nucleotide sequences of certain regions of human DNA that
are unique to individuals)
·
Transcription - (DNA is copied to make a
complementary strand of RNA)
·
Gene therapy - (Gene replaces or repairs a mutated
(changed) gene inside the body's cells to help prevent or treat certain
diseases, such as cancer.)
·
Mutations - (Alteration
in the genes or chromosomes of a cell)
Structure of RNA:-
·
RNA is a single stranded and it
is made up from ribonucleotides and
they are linked by phosphodiester bonds.
· A
ribonucleotide in the RNA chain contains ribose pentose sugar), one of the four
nitrogenous bases (A, U, G, and C), and a phosphate group.
·
The minute structural difference between the sugars
gives DNA
stability,
making DNA more
suitable for storage of genetic
information, whereas the relative instability of RNA makes it
more suitable for its more short-term functions.
·
The RNA-specific pyrimidine uracil forms a complementary base pair with
Adenine and is used instead of the
thymine used in DNA.
· RNA
is single stranded, most types of RNA molecules show extensive intramolecular base
pairing between complementary sequences within the RNA
strand, creating a predictable three-dimensional structure essential for their
function
Functions of RNA
RNA is involved in many functions and is found
easily in living organisms, including viruses, plants, bacteria and animals.
Ø Here
are the primary functions of RNA-
· Create
proteins via
translation process.
· It promotes DNA translation into
proteins
·
It acts as an adapter molecule during
protein synthesis
·
It functions as messenger between ribosomes and DNA
·
RNA is carries of all genetic information which translated by
ribosome into various proteins.
·
mRNA, rRNA, and tRNA are the three main types of RNA involved in protein synthesis
·
They are primary genetic material for
viruses.
·
RNA allows ribosomes to pick
the right amino acid
Copying DNA/ DNA Replication
(Semi conservative model)
·
When DNA is copied, this is called DNA replication.
· Every
double helix in the new generation of an organism consists of one complete “old” strand
and one complete “new” strand
wrapped around each other.
·
A conservative mechanism of replication proposes
that the
old DNA is used as a template only and is not
incorporated into the new double-helix. Thus the new cell has one completely
new double-helix and one completely old double-helix.
·
The hydrogen bonds holding together paired bases are broken and the
molecule is split in half, the legs of the ladder are separated.
·
This gives two single strands. New strands are formed by matching the
bases (A with T and G with C) to make the missing strands.
·
An enzyme called DNA
helicase splits the DNA down the middle by breaking the hydrogen bonds.
·
Then DNA molecule breaks in two separate pieces, another molecule
called DNA polymerase and they
makes a new strand they matches each of the strands of the split DNA molecule.
·
All of copied DNA molecule is made from half of the original (starting)
molecule and half of new bases.
·
Semiconservative replication would
produce two copies that each contained one of the original strands of DNA and
one new strand.
·
Semiconservative replication is beneficial to DNA repair. During
replication, the new strand of DNA adjusts to the modifications made on the
template strand.
Mutations
When DNA is copied, mistakes are
sometimes made – these are called mutations. There are four
main types of mutations:
·
Deletion, where one or more bases are left
out.
·
Substitution, where one or more bases are
substituted for another base in the sequence.
·
Insertion, where one or more extra base is put
in.
·
Duplication on, where a sequence of bases pairs are
repeated.
o Mutations may be classified
by their effect on the structure and function of proteins, on fitness.
o Mutations effect on
organism may be, bad / neutral/benefit.
o Sometimes mutations causing death for the organism – because the protein made by the new DNA fail (not work), causes the embryo to die and other hand, evolution (changes in the genetic material) is moved forward by mutations, when the new version of the protein works better for the organism.
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