Briefly describe Polymorphism.

1. The Search for Genetic Material:

(i) Nucleic acids are organic molecules that carry genetic information in all living organisms.

(ii) Friedrich Miescher, a Swiss biochemist, was first to isolate nucleic acids from the nucleus of pus cells in 1869. He called it nuclein. Altman coined the term 'Nucleic acid' in 1889.

(iii) Two kinds of nucleic acids are recognized in living cells – DNA and RNA.

(iv) DNA is found in all organisms except a few viruses. The greatest amount of DNA is concentrated in the nucleus. It also occurs in cell organelles like mitochondria, plastids, and centrioles.

(v) RNA is found in all living cells. In most plant viruses and few animal viruses, it is the genetic material.

(vi) Frederick Griffith ($1928$) reported the genetic transformation of Streptococcus pneumoniae (causative agent of pneumonia).

(vii) Oswald Avery, Colin MacLeod, and Maclyn McCarty ($1944$) found that the 'transforming principle' was DNA alone.

(viii) The experiments of Alfred Hershey and Martha Chase ($1952$) on the bacteriophage (virus) $T2$finally proved that DNA is the genetic material and not protein.

(ix) The DNA replicates semi-conservatively; the complementary H-bonding guides the process.

(x) Matthew Meselson and Franklin Stahl ($1958$) provided strong evidence for the semi-conservative model of DNA replication in Escherichia coli.

2. The RNA world:

(i) DNA stores genetic information, and RNA mostly helps transfer and express information.

(ii) RNA consists of adenine, guanine, cytosine, and uracil.

(iii) Though DNA and RNA both function as genetic material, DNA being chemically and structurally more stable, is a better genetic material.

(iv) RNA is the first to evolve, and DNA was derived from RNA.

3. DNA Packaging in Eukaryotes:

(i) In eukaryotes, this organization is much more complex and is carried out by a set of positively charged basic proteins called histones.

(ii) Histones are rich in the basic amino acid residues lysine and arginine with charged side chains. There are five types of histone proteins i.e., H1,H2A,H2B,H3 and H4

(iii) Four occur in pairs to produce histone octamer or nu-body (two copies of each H2A, H2B, H3 & H4).

(iv) The negatively charged DNA is wrapped around the positively charged histone octamer to form a nucleosome structure.

4. DNA replication:

(i) The hallmark of the double-stranded helical structure of DNA is the hydrogen bonding between the bases from opposite strands.

(ii) Adenine pairs with Thymine through two H-bonds and Guanine with Cytosine through three H-bonds; this makes one strand complementary to the other.

(iii) Chargaff's rule: According to Erwin Chargaff ($1950$), the percentage of adenine (A) is equal to the percentage of Thymine (T), and the percentage of guanine (G) is equal to the percentage of cytosine (C).

(iv) On the basis of Chargaff's chemical data, Wilkin's and Franklin's X-ray diffraction data,, James Watson and Francis Crick proposed the three-dimensional structure of DNA.

(v) The 'Central dogma' of molecular biology was initially formulated in $1958$ by Crick stating that the biological information flows in the unidirectional pattern: DNA —> RNA —> Protein.

(vi) During cell division, DNA makes its copies by the process of DNA replication.

(vii) Replication fork, Primer binding, Elongation and Termination are the four replication steps.

5. Transcription:

(i) Temin and Baltimore ($1970$) discovered the enzyme reverse transcriptase or RNA-dependent DNA polymerase.

(ii) The process of copying genetic information from one strand of the DNA into RNA is termed "transcription".

(iii) The strand that has the polarity 3'→5' acts as a template and is called a template strand or a non–coding strand.

(iv) The other strand with polarity 5'→3' and the sequence same as RNA, except Thymine at the place of uracil, is displaced during transcription, and this strand is called the coding strand or sense strand, or non-template strand.

(v) A transcription unit in DNA is defined primarily by three regions in the DNA: a promoter, the structural gene, and a terminator.

(vi) A segment of DNA that codes for RNA may, in a simplistic term, be referred to as a gene.

(vii) During transcription, one of the DNA strands acts as a template to direct the synthesis of complementary RNA.

(viii) In prokaryotes, the transcribed mRNA is functional, hence can directly be translated.

(ix) The eukaryotic gene is split into coding regions called exons and non-coding regions called introns.

(x) The coding sequences, exons, are interrupted by non-coding sequences, introns.

(xi) Introns are removed, and exons are joined to produce functional RNA by splicing.

(xii) The messenger RNA contains the base sequences that are read in a combination of three (to make triplet genetic code) to code for an amino acid.

6. Genetic code:

(i) The correspondence between triplets in DNA (or RNA) and amino acids in a protein are known as genetic code.

(ii) The genetic code is read again on the principle of complementarity by tRNA that acts as an adapter molecule.

(iii) A table of all the code words or codons that specify amino acids is termed as a coding dictionary.

(iv) AUG which code for methionine (Met) is used as the start signal in protein synthesis and is the most common initiation codon.

(v) Three triplets UAA (ochre), UAG (amber) and UGA (opal), do not code for amino acids and are called nonsense codons.

(vi) mRNAs in prokaryotes often have several coding regions (polycistronic mRNA), while the eukaryotic mRNA has only one coding region (monocistronic mRNA).

(vii) There are specific tRNAs for every amino acid.

7. Translation:

(i) Translation refers to the process of polymerisation of amino acid to form a polypeptide.

(ii) Aminoacylation refers to the process of attachment of amino acid to a tRNA.

(iii) mRNA also has some unnecessary sequences that are not translated and are referred to as untranslated regions.

8. Regulation of Gene Expression:

(i) Regulation of gene expression refers to a very broad term that may occur at various levels. Considering that gene expression results in the formation of a polypeptide, it can be regulated at several levels.

(ii) In eukaryotes, the regulation could be exerted at transcriptional level, processing level, Transport of mRNA from nucleus to cytoplasm and translational level.

(iii) Francois Jacob (a geneticist) and Jacques Monod (a biochemist) proposed a model of gene regulation, known as operon model in bacteria in 1961.

(iv) Operon is a co-ordinate group of genes such as structural gene, operator gene, promoter gene, regulator gene which function together and regulate a metabolic pathway as a unit, e.g., lac-operon, trp-operon, ara-operon, his-operon, val-operon etc.

9. Human Genome Project and DNA fingerprinting:

(i) Human Genome Project is a global and long-term research effort that aimed to identify, map, and sequence all of the genes in the human genome.

(ii) It identifies all 50,000 to 100,000 genes contained within the genome and provides research tools to analyse all of this genetic information.

(iii) DNA fingerprinting is a technique to find out variations in individuals of a population at the DNA level. It works on the principle of polymorphism in DNA sequences.

(iv) Practical Applications of DNA fingerprinting are paternity–maternity disputes, criminal identification and forensics, personal identification, and close relations of an intending immigrant.