DEFINITIONGenetic mutations can be defined as new, sudden or induced inheritable discontinous/ continous changes or variations caused by a change in the

nucleotide type.It may be a change in the sequence of DNA segment representing a gene or cistron. Extragenous mutations: The first scientific study of gene mutations started with the discovery of white eye trait in DROSOPHILA by Morgan in 1910. Muller and Stadler (1927)- that X-ray induced mutation All genes can mutate. The direction of mutations is not predictable. Most of the mutations are recessive allelic mutations and involve a loss of gene-function. Gene mutations1)Spontaneous 2)Induced Organisms possess mutator and anti-mutator genes. Mutator genes cause mutations by altering polymerase activity. Anti-mutator genes check the alterations in nucleotide sequence during replication of DNA.

SPONTANEOUS MUTATIONS
Mutations that occur randomly, naturally and automatically due to internal modifications i.e. with out any external factor influence. Rate of spontaneous mutations varies from 1 to 2000 to 1 in several million divisions. Mechanism of spontaneous mutations: Transistions may be produced by Tautomeric shift or ionization of bases, which leads to mistaken base pairing. All 4 nitrogen bases occur in their tautomeric state. The alternate bases are formed by intra-molecular rearrangement in their tautomeric state. The alternate bases are formed by intra-molecular rearrangement in the distribution of Hatom. e.g. Keto form changed to enol form; amino form changed to imino form. If DNA has tautomer of adenine, during replication- it pairs with cytosine instead to thymine.

Deamination of basesDue to deamination, there is alteration in resting nucleic acid. Cytosine- uracil Adenine-hypoxanthine Guanine-xanthine

COPY ERRORThere are a number of steps involved in replication, transcription and translation. Any entry of a different group will cause mutation. Most of the copy errors are corrected during proof reading but a few do escape correction.

INDUCED MUTATIONS
They are mutations that are produced in response to specific external factors and chemicals. Muller (1927) was first to produce induced mutations in Drosophila by exposing them to X-rays. The specific factors and chemicals of the environment that induce mutations are called mutagens. MUTAGENSPHYSICAL: 1) low pH Under pH below 4, some bases become positively charged and strand separation occurs can be lethal. 2) High temp. Rise in temperature breaks the hydrogen bonding between the two strands of DNA and hence denatures the later. It disturbs the synthetic process connected with replicaton and transcription. Increase in temperature increases rate of mutation. 3) High energy radiations Include neutrons, alpha particles, cosmic rays, gamma particles, beta particles. Xrays, U.V rays etc. U.V rays are non-ionizing radiations which affect DNA by forming thymine dimers. It causes bends in DNA duplex that bring about mis-replication. Other high energy radiations are ionizing radiations. They ionize DNA constituents that can react with several biochemicals. X-rays are known to deaminate and de-hydroxylate nitrogen bases, forming peroxides. Zperoxides in turn oxidize the deoxyribose.