mutation by rusha chakraborty

1. Mutations

2. Definition
• A mutation is a sudden change in the
genetic material of a cell that can be
passed on from the cell to its daughter
cells during the process of cell division.

3. • Mutations are important for several
reasons.
• First mutations are the source of new
variation important for evolution.
• Mutations are considered to be one of
the ways that evolution happens.

4. • Mutations can lead to various human
medical conditions.
• Mutations can happen on a number of
different scales.
• Mutations involving only a single base
pair in a DNA molecule are called point
mutations.

5. Somatic vs germ cell mutations
• In multicellular organisms such as plants
or animals mutations may occur in the
somatic cells of the organism.
• Somatic cells are the cells involved in
growth and repair and maintenance of
the organism.

6. • A mutation in these cells may lead to
cancer and certain types of chromosomal
mutations may be involved in aging.

7. • Other mutations happen in the germ
cells
• These mutations may appear in the
gametes and then in the offspring
produced by sexual reproduction
• These sorts of mutations are called germ
cell/line mutations.

8. Causes of mutations
• Mutations are often classified as:
1. Spontaneous and
2. Induced

9. • Spontaneous mutations are mutations
which arise because of errors in the DNA
duplication process.

10. • As part of this process there is a proof
reading mechanism involving one of the
DNA polymerases.
• But this process is not 100% perfect, leading
to a low level of mutations per generation.

11. • For humans this mutation rate is about 1 x
10-6 mutations per gene locus per
generation.
• This means that it is likely that most of us are
carrying at least one new mutation not found
in our parents.

12. • Induced mutations are mutations
brought about by exposure to chemicals
or various forms of radiation.
• These are called as Mutagens

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Two main types of Mutations
–Spontaneous mutations
•Result from abnormalities in
biological
processes
•Underlying cause lies within the cell
–Induced mutations
•Caused by environmental agents
•Cause originates outside of the cell

14. 14
• Causes of spontaneous mutations
–Abnormalities in crossing over
–Aberrant segregation of chromosomes during
meiosis
–Mistakes by DNA polymerase during
replication
–Alteration of DNA by chemical products of
normal metabolic processes
–Integration of transposable elements
–Spontaneous changes in nucleotide structure

15. 15
• Induced mutations are caused by
mutagens
–Chemical substances or physical agents
originating outside of the cell
–Enter the cell and then alter the DNA
structure

16. 16
CAUSES OF MUTATIONS

17. 17
CAUSES OF MUTATIONS
• Spontaneous mutations are random
events
–Not purposeful
–Mutations occur as a matter of chance
• Some individuals possess beneficial mutations
– Better adapted to their environment
– Increased chance of surviving and reproducing
• Natural selection results in differential
reproductive success
– The frequency of such alleles increases in the
population

21. Types of Mutations
• Transitions
• Transversions Point Mutations
• Frameshift mutations
• These types are observed under spontaneous
mutations
Substitution
Mutations

22. Mechanism of spontaneous mutation
• Proposed by Watson & Crick
• Structures of bases in DNA are not static
• H atoms can move from one position to
another (from an amino group to a ring
Nitrogen) – tautomeric shifts
• Can alter pairing potential of the bases

24. Keto Enol

25. • Thymine and Guanine – more stable keto
forms
• Adenine and Cytosine – more stable
amino forms
• Tautomeric shifts – less stable enol and
imino forms respectively (infrequently)

26. • Bases are expected to be in their less stable
tautomeric forms for only very short periods
of time
• If the base existed in the rare form at the time
of replication results in a mutation
• adenine-cytosine and guanine-thymine base
pairs
• AT to GC or a GC to AT base pair substitution

30. • Mutations resulting from tautomeric shifts in
the bases of DNA involve the replacement of a
purine in one strand of the DNA with the
other purine OR replacement of a pyrimidine
in the complementary strand with the other
pyrimidine
• Such base pair substitutions are called
transitions

31. • Base pair substitutions involving the
substitution of a purine for a pyrimidine and
pyrimidine for a purine are called
transversions

33. Effects substitution mutations
• Substitution mutations may vary in effect on
the polypeptide resulting from translation.
• Silent mutation the mutation does not alter
the polypeptide at all.
• While, nonsense mutations may lead to a
radically altered polypeptide.

34. Normal
TAC GTG ATA CCA AAG TAG ACT
AUG CAC UAU GGU UUC AUC UGA
met his tyr gly phe ile -

35. Missense mutation
TAC GTG ATA GCA AAG TAG ACT
AUG CAC UAU CGU UUC AUC UGA
met his tyr arg phe ile -

36. Normal
TAC GTG ATA CCA AAG TAG ACT
AUG CAC UAU GGU UUC AUC UGA
met his tyr gly phe ile -

37. Nonsense Mutation
TAC GTG ATT CCA AAG TAG ACT
AUG CAC UAA GGU UUC AUC UGA
met his - - - - -

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EFFECTS OF MUTATIONS
• Nonsense mutations
–Normal codon is changed into a stop
codon
• e.g., AAA  AAG (lys  stop)
–Translation is prematurely terminated
• Truncated polypeptide is formed
–Protein function is generally affected

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EFFECTS OF MUTATIONS
• Missense mutations
– Amino acid sequence is altered
• e.g., GAA GTA (glu  val)
– Phenotype may be affected

41. Normal
TAC GTG ATA CCA AAG TAG ACT
AUG CAC UAU GGU UUC AUC UGA
met his tyr gly phe ile -

42. Neutral mutation
TAC GTG ATA CGA AAG TAG ACT
AUG CAC UAU GCU UUC AUC UGA
met his tyr ala phe ile -

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EFFECTS OF MUTATIONS
• Neutral mutations
–Type of missense mutation
–Amino acid sequence is altered
• e.g., CTT ATT (leu  ile)
• e.g., GAA GAC (glu  asp)
–No detectable effect on protein function
• Missense mutations substituting an amino
acid with a similar chemistry to the original
is likely to be neutral

44. Normal
TAC GTG ATA CCA AAG TAG ACT
AUG CAC UAU GGU UUC AUC UGA
met his tyr gly phe ile -

45. Silent mutation
TAC GTG ATA CCG AAG TAG ACT
AUG CAC UAU GGC UUC AUC UGA
met his tyr gly phe ile -

46. • Addition or deletion of one or a few base pairs
- collectively referred to as frameshift
mutations

47. The effects of frameshift mutation
• In frameshift mutations, since a base is
either added or removed from a codon,
the effect is to shift the codons as read
during translation by one position which
radically alters the meaning of the mRNA
in terms of how it is translated..

48. • Frameshift mutation changes all the
amino acids after the first one because
codons are in groups of three non
overlapping RNA bases.

50. • If messenger RNA resulting from the original DNA can
be thought of as the following string of letters decoded
by reading each group of three non overlapping
letters:
THEBIGCATATETHERAT = THE BIG CAT ATE THE RAT
If the third letter(E) in the string is deleted we have:
THBIGCATATETHERAT = THB IGC ATA TET HER AT
which makes no sense when decoded.

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EFFECTS OF MUTATIONS