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Similar to mutation-causes,types ,mechanism and uses
mutation-causes,types ,mechanism and uses
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- 2. Any suddenchange occurring in hereditary material is called as mutation They may be harmful, beneficial or neutral
- 3. In multicellularorganism, two broad categories of mutations: Somatic mutations & germ line mutations
- 4. Somatic mutations Arisein the somatic cells Passed on to other cells through the process of mitosis Effect of these mutations depends on the type of the cell in which they occur & the developmental stage of the organism If occurs early in development, larger the clone of the mutated cells
- 5. Germ line mutations They occur in the cells that produce gametes Passed on to future generations In multicellular organisms, the term mutation is generally used for germ line mutations
- 6. Some Facts Termmutation was given by Devries in 1901 while studying evening primerose Oenothera lamarckiana Most of these were chromosomal variations Some were point variations Originally the term mutation was given to both chromosomal as well as point mutations
- 7. Cont. Recently chromosomalmutations are studied separately The term mutation is now given only to point mutations
- 8. Definition DNA isa highly stable molecule that replicates with amazing accuracy Some errors of replication do occur A mutation is defined as an inherited change in genetic information
- 9. Types of genemutation Number of ways to classify gene mutations: On the basis of the molecular nature of the defect On the nature of the phenotypic effect-- amino acid sequence of the protein is altered or not On the basis of the causative agent of the mutation
- 10. Mutations on thebasis of the molecular nature of the defect: Base substitution Insertions & deletions
- 11. Base substitution: Simplesttype of gene mutation Involves the alteration of a single nucleotide in the DNA
- 12. A base substitutionusually leads to base pair substitution GGG AGT GTA GAT CGT CCC TCA CAT CTA GCA CCC TCA CAT CTA GCA GGG AGT GCA GAT CGT A base substitution CCC TCA CGT CTA GCA GGG AGT GCA GAT CGT GGG AGT GTA GAT CGT CCC TCA CAT CTA GCA First cycle of DNA replication
- 13. Base substitution isof two types: Transition: Purine is replaced with a purine Pyrimidine is replaced with a pyrimidine A T T C C G G A
- 14. Transversions: A purine isreplaced by a pyrimidine A C A T G G C T C G C A T G T A or a pyrimidine is replaced by a purine
- 15. The number ofpossible transversions is twice the number of possible transitions But Transitions are usually more frequent in vivo
- 16. Insertions & deletions: 2nd major class of gene mutation Addition or the removal, respectively, of one or more nucleotide pair Usually changes the reading frame, altering all amino acids encoded by codons following the mutation Also called as frame shift mutations
- 17. cont. Additions ordeletions in the multiples of three nucleotides will lead to addition or deletion of one or more amino acids These mutations are called in-frame insertions and deletions, respectively.
- 18. Mutations on thebasis of the Phenotypic effects of mutations: Most common phenotype in natural populations of the organism is called as wild type phenotype The effect of mutation is considered with reference to wild type phenotype
- 19. Forward mutation: amutation that alters the wild type phenotype Reverse mutation (reversion): a mutation that changes a mutant phenotype back in to the wild type
- 20. Missense mutation: abase is substituted that alters a codon in the mRNA resulting in a different amino acid in the protein product TCA AGT UCA TTA AAT UUA Ser Leu
- 21. Nonsense mutation: changesa sense codon into a nonsense codon. Nonsense mutation early in the mRNA sequence produces a greatly shortened & usually nonfunctional protein TCA AGT UCA TGA ACT UGA Ser Stop codon
- 22. Silent mutation: altersa codon but due to degeneracy of the codon, same amino acid is specified TCA AGT UCA TCG AGC UCG Ser Ser
- 23. Neutral mutation: mutationthat alters the amino acid sequence of the protein but does not change its function as replaced amino acid is chemically similar or the affected aa has little influence on protein function. CTT GAA CUU ATT TAA AUU Leu Ile
- 24. Loss of functionmutations: Complete or partial loss of the normal function Structure of protein is so altered that it no longer works correctly Mutation can occur in regulatory region that affects transcription , translation or spilicing of the protein Frequently recessive
- 25. Gain of functionmutations: Produces an entirely new trait Causes a trait to appear in inappropriate tissues or at inappropriate times in development Frequently dominant
- 26. Conditional mutations: Expressedonly under certain conditions Lethal mutations: Cause the death of the organism
- 27. Suppressor mutation: Suppressesthe effect of other mutation Occurs at a site different from the site of original mutation Organism with a suppressor mutation is a double mutant but exhibits the phenotype of un mutated wild type Different from reverse mutation in which mutated site is reverted back into the wild type sequence
- 28. On the basisof Causative agent of mutation: Spontaneous: Mutations that result from natural changes in DNA Induced: Results from changes caused By environmental chemicals & radiations Any environmental agent that increases the rate of mutation above the spontaneous is called a mutagen such as chemicals & radiations
- 29. Chemical Mutagens: Firstdiscovery of a chemical mutagen was made by Charlotte Auerbach Base Analogs: Chemicals with structures similar to that of any of the four standard bases of DNA DNA polymerases cannot distinguish these analogs They may be incorporated into newly synthesized DNA molecules
- 30. 5-bromouracil an analog ofthymine N N 1 2 3 6 5 4 O O 5BU Br N N 1 2 3 6 5 4 CH₃ T O O
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- 33. GA C CT G Strand seperation 3’ 5’ 3’ 5’ GA C 3’ 5’ CT G 5’3’ GA C 3’ 5’ CB G 5’ 3’ CT G 5’ 3’ GA C 3’ 5’ GA C 3’ 5’ CB G 5’ 3’ GA C 3’ 5’ CT G 5’ 3’ CB G 5’ 3’ GG C 3’ 5’ CB G 5’ 3’ GG C 3’ 5’ CB G 5’ 3’ GA C 3’ 5’ GG C 3’ 5’ CCG 5’ 3’ replication Incorporated error
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- 35. 2-amino purine (P) Base analog of adenine Normally pairs with thymine May mispair with cytosine Causes a transition mutation
- 36. GT C CA G Strand separation 3’ 5’ 3’ 5’ GT C 3’ 5’ CA G 5’ 3’ GT C 3’ 5’ CP G 5’3’ CA G 5’ 3’ GT C 3’ 5’ GT C 3’ 5’ CP G 5’ 3’ GT C 3’ 5’ CA G 5’ 3’ CP G 5’ 3’ GC C 3’ 5’ CP G 5’ 3’ GC C 3’ 5’ CA G 5’ 3’ GT C 3’ 5’ GC C 3’ 5’ CG G 5’ 3’ replication Incorporated error T.A C.G
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- 39. Both baseanalogs produce transition mutations Mutations by base analogs can be reversed by treatment with the same analog or different analog
- 40. Alkylating agents: Chemicals thatdonate alkyl groups e.g. ehylmethanesulfonate(EMS) It adds an ethyl group to guanine and produces 6- ethylguanine, which pairs with thymine and leads to CG:TA transitions Also adds an ethyl group to thymine to produce 4- ethylthymine, which then pairs with guanine, leading to a TA:CG transition Mutations produced by EMS can be reversed by additional treatment with EMS. Mustard gas is another alkylating agent.
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- 42. Nitrous acid: causesdeamination Cytosine Uracil N N CYTOSINE 1 2 3 6 5 4 NH2 O H N N 1 2 3 6 5 4 O o HNo2 URACIL H
- 43. U G U G U A G C U A U A A T C.G TA C G HNO2 5’3’ 3’ 5’ 5’ 3’ 3’ 5’ 5’ 3’ 3’ 5’ 5’ 3’ 3’ 5’ 3’ 5’ 5’ 3’ 5’ 5’ 3’ 3’ 3’ 5’ 5’ 3’ 3’ 3’ 5’ 5’
- 44. H T H T H C A T H C H C G C A.T G.C A THNO2 5’ 3’ 3’ 5’ 5’ 3’ 3’ 5’ 5’ 3’ 3’ 5’ 5’ 3’ 3’ 5’ 3’ 5’ 5’ 3’ 5’ 5’ 3’ 3’ 3’ 5’ 5’ 3’ 3’ 3’ 5’ 5’ Adenine changes into Hypoxanthin which then pairs with Cytosine
- 45. X C X C X T C G X T X T A T A.T G.C G C HNO2 5’3’ 3’ 5’ 5’ 3’ 3’ 5’ 5’ 3’ 3’ 5’ 5’ 3’ 3’ 5’ 3’ 5’ 5’ 3’ 5’ 5’ 3’ 3’ 3’ 5’ 5’ 3’ 3’ 3’ 5’ 5’ Guanine changes into Xanthin which pairs with Cytosine. Xanthin can also pair with Thymine
- 46. Nitrous acidproduces exclusively transition mutations Both C.G T.A & T.A C.G transitions are produced Thus mutations can be reversed with the nitrous acid
- 47. Hydroxl amine Specificbase modifying mutagen which adds a hydroxyl group to cytosine producing hydroxlamine cytosine which pairs with adenine instead of guanine This Leads to C.G T.A tranisitions Acts only on cytosine thus can not revert the mutation produced
- 48. hC G hC G hC A G C hC A hC A T A T.A C.G C G 5’ 3’ 3’5’ 5’ 3’ 3’ 5’ 5’ 3’ 3’ 5’ 5’ 3’ 3’ 5’ 3’ 5’ 5’ 3’ 5’ 5’ 3’ 3’ 3’ 5’ 5’ 3’ 3’ 3’ 5’ 5’ Cytosine changes into hydroxlamine Cytosine which pairs with Adenine instead of Guanine NH₂OH
- 49. Oxidative reactions: Reactiveforms of oxygen like superoxide radicals, hydrogen peroxide and hdroxyl radicals produced in the course of normal aerobic metabolism or by radiation, ozone, peroxides, and certain drugs Cause damage to DNA & induce mutations by chemical changes Oxidation converts guanine into 8-oxy-7,8- dihydrodeoxyguanine which mispairs with adenine leading to G.C T.A transversion
- 50. Intercalating agents Proflavin,acridine orange, ethidium bromide, and dioxin They are about the same size as a nucleotide They produce mutations by sandwiching themselves (intercalating) between adjacent bases in DNA They distort the three-dimensional structure of the helix and cause single-nucleotide insertions and deletions in replication These insertions and deletions frequently produce frameshift mutations
- 52. Radiations: Ionizing radiations: In1927, Herman Muller demonstrated that mutations could be induced by X-rays. X-rays, gamma rays, and cosmic rays are all capable of penetrating tissues and damaging DNA. They remove electrons from the atoms that they encounter, changing stable molecules into free radicals and reactive ions which then alter the structures of bases and break phosphodiester bonds in DNA. Ionizing radiation also frequently results in double-strand breaks in DNA.
- 53. Mutation rates Thefrequency with which a gene changes from the wild type to a mutant is reffered to as the mutation rate. Expressed as the number of mutations per biological unit i.e. mutations per cell division, per gamete per round of replication e.g. mutation rate for achondroplasia (hereditary dwarfism) is about 4 mutations per 100,000 gametes
- 54. Mutation frequency: Incidenceof a specific type of mutation with in a group of individual organism e.g. for achondroplasia, the mutation frequency in united states is about 2x10⁻⁴
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