MUTATIONS Dr. Madhumita Bhattacharjee Assiatant Professor Botany Deptt. P.G.G.C.G. -11,Chandigarh

Mutations  Any change in the DNA sequence of an organism is a mutation.  Mutations are the source of the altered versions of genes that provide the raw material for evolution.  Most mutations have no effect on the organism, especially among the eukaryotes, because a large portion of the DNA is not in genes and thus does not affect the organism’s phenotype.  Only a small percentage of mutations causes a visible but non-lethal change in the phenotype.

Somatic Vs.Germinal Mutations Some people may have mutations in their skin cells or hair. Such mutations are termed Somatic. Germ mutations occur only in the sex cells& called Germinal Mutations These mutations are more threatening because they can be passed to offspring (forever).

Somatic Mutation Somatic Mutation  In normal body tissue  May have vast effects on individual  Not passed on to offspring  Not of evolutionary significance

Germinal Mutation Germinal Mutation  Germinal or germ line  Gametes or cells producing gametes  Little or no effect on individual originating mutation  Passed on to all cells of zygote formed  Passed on to subsequent generations  Source of new alleles

Mutation  Not necessarily harmful!  Dependent on: 1) nature of mutation 2) environment  Spontaneous  occur randomly throughout genome  rates: /gene/cell  Reversible

Types of Mutations  Point Mutations  Base Pair Substitutions  Silent  Missense – new protein (Amino Acid Substitutions)  Nonsense – stop codon  Base Pair Insertions and deletions  Triplet Repeats  Frameshift Mutations  Variation in Chromosome Number  Variation in Chromosome structure  Deletions  Translocations  Duplications  Inversions

Point mutations  Base subsitution :  neutral  no change in final protein  silent  no change in amino acid  missense  amino acid substitution  nonsense  stop codon substitution

Point Mutations: G C Glu (d) Run-on mutation G C (a) Silent mutation

Point Mutations changes in one or a few nucleotides changes in one or a few nucleotides  Substitution THE FAT CAT ATE THE RAT THE FAT HAT ATE THE RAT  Insertion THE FAT CAT ATE THE RAT THE FAT CAT XLW ATE THE RAT  Deletion THE FAT CAT ATE THE RAT THE FAT ATE THE RAT

Point Mutations  Frameshift Mutations – shifts the reading frame of the genetic message so that the protein may not be able to perform its function.  Insertion THE FAT CAT ATE THE RAT THE FAT HCA TAT ETH ERA T  Deletion THE FAT CAT ATE THE RAT TEF ATC ATA TET GER AT H H

Run-on mutation (can also produce nonsense and run-ons) Summary of Mutation Types

Chromosome Mutations Changes in structure of entire chromosomes  Original Chromosome ABC * DEF  DeletionAC * DEF  DuplicationABBC * DEF  InversionAED * CBF  TranslocationABC * JKL GHI * DEF

Changes in number Of Chromosome  Down Syndrome  Chromosome 21 does not separate correctly.  They have 47 chromosomes in stead of 46.  Children with Down Syndrome develop slower, may have heart and stomach illnesses and vary greatly in their degree of inteligence.

Changes in structure Of Chromosome  Cri-du-chat  Deletion of material on 5 th chromosome  Characterized by the cat-like cry made by cri-du-chat babies  Varied levels of metal handicaps

Sex Chromosome Abnormalities  XYY Syndrome  Normal male traits  Often tall and thin  Associated with antisocial and behavioral problems

What Causes Mutations? There are two ways in which DNA can become mutated:  Mutations can be inherited. Parent to child  Mutations can be acquired.  Environmental damage  Mistakes when DNA is copied

 Spontaneous mutation rate = 1 in 10 9 (a billion) replicated base pairs or 1 in 10 6 ( a million) replicated genes. Mistakes occur during DNA Replication just before cell division. This is natural error rate of DNA polymerase.  Induced Mutations: Caused by mutagens. Mutagens increase mistakes to 10 –5 (100 thousand) or 10 –3 ( a thousand) per replicated gene Spontaneous and Induced Mutation

( Induced Mutation : Mutagens Mutagens are things that cause mutations Chemical mutagens Base pair changers (nitrous acid) Base analogues (e.g.. 5 bromouracil) Frameshift mutagens (aflatoxin, benzpyrene) Radiation X rays, gamma rays break DNA, bases UV light causes knots in DNA strand Many common place items are capable of causing mutations: microwave, fruit from the store, radar, cellular phones….

Chemical Mutagens: Base pair changers (base modifiers) (base modifiers) deaminators like nitrous acid, nitrosoguanidine, or alkylating agents like cytoxan deaminators like nitrous acid, nitrosoguanidine, or alkylating agents like cytoxan Incorporated as a “T” Base analogues “mimic” certain bases but pair with others - E.g. 5-fluorouracil, cytarabine Acts like a “C” cytarabine cytoxan Nitrous acid

 Ionizing radiation (X rays, gamma rays, UV light) : causes the formation of ions that can react with nucleotides and the deoxyribose- phosphate backbone.  Nucleotide excision repairs mutations Ionizing Radiations as mutagens

X-rays and Gamma Rays Cause Breaks in DNA

 UV radiation causes thymine dimers, which block replication.  Light-repair separates thymine dimers  Sometimes the “repair job” introduces the wrong nucleotide, leading to a point mutation. Ionizing Radiation: UV Figure 8.20

Significance of Mutations Most are neutralMost are neutral Eye colorEye color Birth marksBirth marks Some are harmfulSome are harmful Sickle Cell AnemiaSickle Cell Anemia Down SyndromeDown Syndrome Some are beneficialSome are beneficial Sickle Cell Anemia to MalariaSickle Cell Anemia to Malaria Immunity to HIVImmunity to HIV