Transcript Gene Mutations - ASAB-NUST

Causes of Mutations
 Mutations result from both internal and
external factors
 Spontaneous Mutations : Those that are a
result of natural changes in DNA structure
 Induced Mutations : result from changes
caused by environmental chemicals or
radiation
Categories of Mutations
 In multicellular organisms there are two broad
categories of mutations:
 Somatic mutations:

Arise in somatic tissues which do not
produce gametes
 Germline mutations:


Arise in cells that ultimately produce
gametes
These mutations can be passed to future
generations
There are two basic classes of mutations: somatic
mutations and germ-line mutations
Types of Gene Mutations
 Number of ways to classify gene mutations
 Some classification schemes are based on the
nature of the phenotypic effect
 Base substitutions
 Insertions and deletions
Base Substitutions
 Alternation of a single nucleotide in the DNA
 Complementary
strands
nature
of
the
two
DNA
 When the base of one nucleotide is altered,
corresponding nucleotide on the opposite
strand will be altered in the next round of
replication
 Leads to a base-pair substitution
Types of Base Substitution
 Base substitutions are of two types:
 Transition:
 A purine is replaced by a different purine
or, alternatively a pyrimidine is replaced by
a different pyrimidine
 Transversion:
 A purine is replaced by a pyrimidine or a
pyrimidine is replaced by a purine.
 Number of possible transversions is twice
the number of possible transitions, but
transitions usually arise more frequently
A transition is the substitution of a purine for
a purine or a pyrimidine for a pyrimidine; a
transversion is the substitution of a
pyrimidine for a purine or a purine for a
pyrimidine
Insertions and Deletions
 Second major class of gene mutations contains
insertions and deletions
 Addition or the removal of one or more
nucleotide pairs
 Insertions and deletions are more frequent
Insertions and Deletions
 Frameshift mutations:
 Insertions and deletions often lead to a
change in the reading frame of a gene
 Sequences that encode proteins may
lead to frameshift mutations changes in
the reading frame
 Frameshift mutations generally have
drastic effects on the phenotype
 Addition or removal of one or more amino
acids may still affect the phenotype
 These mutations are called in-frame
insertions and deletions
Phenotypic Effects of
Mutations
 The effect of a mutation must be considered
with reference to a phenotype against which
the mutant can be compared
 Forward Mutation: A mutation that alters the
wild-type phenotype
 Reverse Mutation (a reversion): changes a
mutant phenotype back into the wild type
Phenotypic Effects of
Mutations
 Missense Mutation: base substitution that
alters a codon in the mRNA, resulting in a
different amino acid in the protein
 Nonsense Mutation: changes a sense codon
(one that specifies an amino acid) into a
nonsense codon (one that terminates
translation)
Phenotypic Effects of
Mutations
 Silent Mutation: Alters a codon but due to the
redundancy of the genetic code, the codon
still specifies the same amino acid
 Neutral Mutation: is a missense mutation that
alters the amino acid sequence of theprotein
but does not change its function.
 It occurs when one amino acid is replaced by
another that is chemically similar or when the
affected amino acid has little influence on
protein function
Phenotypic Effects of
Mutations
 Loss-of-function
Mutations:
cause
the
complete or partial absence of normal
function.
 A loss-of-function mutation so alters the
structure of the protein
 Gain-of-function
Mutation: produces an
entirely new trait or it causes a trait to
appear
inappropriate
tissues
or
at
inappropriate times in development
Base substitutions can cause (a) missense, (b) nonsense, and (c)
silent mutations
Phenotypic Effects of
Mutations
 Conditional mutations: which are expressed
only under certain conditions
 Lethal
death
Mutations: which cause premature
Phenotypic Effects of
Mutations
 Suppressor Mutation: is a genetic change that
hides or suppresses the effect of another
mutation. This type of mutation is distinct
from a reverse mutation, in which the mutated
site changes back into the original wild-type
sequence
Relation of forward, reverse, and suppressor mutations
Mutation Rates
 The frequency with which a gene changes
from the wild type to a mutant
 Expressed as the number of mutations per
biological unit, which may be mutations per cell
division, per gamete, or per round of
replication