Molecular Genetics 1

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Molecular Genetics

The Genetic/Molecular Basis of

Inheritance


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DNA

Polymer containing chains of nucleotide

monomers i.e., Polynucleotide


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Nucleotide

sugar + base + phosphate


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Sugar

2 deoxyribose i.e., -OH group on carbon 2of ribose replaced by H

5 carbon ring

Base attached to the 1 carbon of thedeoxyribose


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Base

Purines : two carbon-nitrogen ringsAdenine

Guanine

Nitrogen at position 9 of the ring

Pyrimidines : single carbon nitrogen ring

Thymine

Uracil

Cytosine


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Nucleoside

A sugar + Base


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Phosphate group

Nucleotide has 1 or 2 or 3 phosphate

groups (PO ) attached to the 5

carbon of the sugar4


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Nucleotides

Nucleotides occur as individual molecule orpolymerized as DNA or RNA


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DNA Polynucleotide

Nucleotide triphosphate

Two phosphates are lost during

polymerization

Nucleotides joined by remaining

phophate


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Phosphodiester bond between 5phosphate

of one nucleotide and 3 hydroxyl of thenext nucleotide

Therefore, polynucleotide has a free 5

phosphate at one end (5 end) and a free3OH (3end) at the other end

DNA Polynucleotide


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Two polynucleotide strands wrapped around

each other to form double helix

Sugar phosphate part of molecule forms a

backbone

Base face inwards and stacked on top ofeach other

Two polynucleotide chains run in opposite

direction

The Double Helix


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Right Handed

Executes a turn every 10 bases

Major groove interacts with proteins

Variant DNA structure identified including ZDNA having left handed helix

The Double Helix


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Complementary base pairing

Hydrogen bonds between bases on the two

DNA strands stabilize the double helix

Purine always with pyrimidine

Therefore, A with T or U and G with C

The Double Helix


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Advantages of Complementary base pairing

Allows genetic information to be preservedduring replication of DNA and expression of

genes

Separation of two strands by heat or

chemicals or action of enzymes

The Double Helix


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Thymine replaced by Uracil

2deoxyribose replaced by ribose

Exists as a single polynucleotide strand

RNA Structure


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A unit of information

Corresponds to a discrete segment of DNAthat encodes the amino acid sequence of a

polypeptide

In humans about 30,000 genes arranged on

23 chromosomes

Gene


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Dispersed and separated by noncodingintergenic DNA In humans genes sequence

account for less than about 30% of the total

DNA

Gene


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Information encoded on the template strand or

antisense strand or noncoding strand which

directs the synthesis of an RNA molecule

The other strand is called nontemplate strand

or sense strand or coding strand

Both DNA strands can act as the template

strand

Gene


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Genes vary greatly in size from less than 100

bases pairs to several million base pairs

Gene


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Most genes spread out randomly along

chromosomesSome organized into groups or clusters

Operons in bacteria and multigene families

in higher organism

Gene families


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Lac operon in E.coli

Codes for enzymes required by thebacterium to break down lactose

Allows to be switched on or off at the same

time allowing the organism to use its

resources efficiently

Gene families


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Genes are identical or very similar

Not regulated coordinately

Probably reflects a requirement for multiple

copies of that gene fulfilled by evolution

May exist as separate clusters on different

chromosomes

Multigene families


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May be simple or complex

Simple multigene families have identical genes

e.g., gene for the 56 ribosomal RNA, there areabout 2000 clustered copies of this gene

Complex multigene families contain genes that

are very similar but not identical e.g., Genes

that encode protein chains found in

hemoglobins

Multigene families


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Transcription

Process of transfer of information by DNA

directing the synthesis of mRNA molecule of

complementary sequence

Gene expression


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Translation

Process of mRNA directing the synthesis of apoly peptide bases on base sequence of the

mRNA

The amino acid sequence of the proteindetermines its three dimensional structure

which in turn dictates its function

Gene expression


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The transfer of information can only occur in

one direction from DNA to RNA to proteinand cannot occur in reverse

Exception reverse transcriptase enzyme

found in retroviruses which can copy RNAinto DNA

The Central Dogma


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Structural features of a typical human

gene

Gene promoters

Gene enhancers Gene silencers

Locus controlled regions

Gene


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Expression of genes is regulated by a

segment of DNA sequence present upstream

of the coding sequence is known as promoter

Gene promoters


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DNA sequence gene in promoters are

conservedRecognized and bound by the RNA

polymerase and other associated proteins

called transcription factors that bring aboutthe synthesis of an RNA transcript of the gene

Gene promoters


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Exons : Coding segments of DNA of a gene

Introns : Interspersed noncoding segments ofDNA of a gene

Before the biological information in a gene

can be used to synthesise a protein, theintrons must be removed from RNA

molecules by splicing leaving only the coding

information of exons in continuity

Introns and Exons


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Copies of some genes which contain

sequence errors acquired during evolution

whereby rendering them non functional areknown as pseudogenes.

Represent evolutionary relics of original

genes

Examples : Several globin pseudogenes

present in the globin gene clusters

Pseudogenes


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Gene Expression

Genetic information coded in the basesequences of DNA molecules as a series

of genes

Gene expression term describes how

cells decode the information to synthesizeproteins required for cellular function


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It involves the synthesis of a complementary

RNA molecule whose sequence specifies the

amino acid sequence of a protein

For every gene the DNA sequence is

collinear with the amino acid sequence of the

polypeptide it encodes

Gene Expression


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5 -3 base sequence of the coding strand

specifies the amino acid sequence of theencoded polypeptide from the amino to

carboxy terminus

Gene Expression


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It describes how base sequences are

converted into amino acid sequences duringprotein synthesis

DNA sequence of a gene divided into a

series of units of three bases

Genetic Code


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Each set of three bases is called is called a

codon

It specifies a particular amino acid

The four bases in DNA and RNA can

combine as a total of 4 = 64 codonsThey specify the 20 amino acids found in

proteins

Codon

3


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Degeneracy or the redundancy of the genetic

codeAmino acid having more than one codon

Exception : Methionine and tryptophan

Codon


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Synonyms : Codons which specify the same

amino acids and tend to be similarVariations between synonyms tend to occur

at the third position of the codon, known as

the wobble position

This minimizes the effects of mutations

Codon


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Of the 64 possible codons, 61 code for amino

acids

The remaining three, UAG, UGA, and UAA act

as signals for protein synthesis to stop :

Termination codons or stop codons

Codon


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AUG the codon for methionine, is the signal

for protein synthesis to start : initiation codon

All polypeptides start with methionine, may be

removed subsequently

Codon


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Each set of codons is known as a reading

frame

Depending on which base is chosen as the

start codon, three possible sets of codons

may be read from any base sequence

Reading Frames


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The initiation codon determines the reading

frame of a protein coding sequence

Usually other reading frames tend to contain

stop codons and are not used for protein

synthesisAn open reading frame is a sequence of

codons bounded by start and stop codons

Reading Frames


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The genetic code applies universally with all

organisms using the same codons for each

amino acid

Exception : Mitochondrial genomes and

some unicellular organisms For example inmitochondria, UGA, a termination codon,

codes for tryptophan

Universality of the code


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Copy of DNA produced prior to division of cell

DNA is copied 5 3 by DNA polymeraseusing single stranded DNA as a template

Replication semiconservative

In E. coli, DNA polymerases I and III have 3

5 exonuclease activity proofread

sequences ensuring a very low error rate

DNA replication


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DNA synthesis occurs at the replicaton fork

A helicase separates the double helixA single strand binding (SSB) protein keeps

strand separate

DNA synthesized continuously on the leading

strand

The replication fork


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Discontinuously as segments (Okazaki

fragments) on the lagging strand

DNA polymerase alpha initiates DNAsynthesis

DNA polymerase delta and alpha synthesize

respectively leading and lagging strand

DNA ligase joins the Okazaki fragments by a

phosphodiester bond

The replication fork


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Chromosomes replicated from multiple origins

Replication bubbles form and merge

eventually

Transcriptionally active regions replicated first

Repication requires DNA to be unwound fromnucleosomes

DNA Replication


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Special mechanisms required to replicate the

ends of chromosomes

Telomerase adds noncoding sequence that

allows replication of chromosome ends

DNA Replication


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Molecular Genetics 1

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