Download Biology 331: Chapter 15

Biology 331: Chapter 15
Gene Mutation
Introduction:
Mutation:

The inherent tendency of organisms to change from one
hereditary state to another
Gene Mutation (Point mutation):

When a gene changes from one allele to another
Chromosome Mutation:

Segments of chromosomes, chromosomes or sets of
chromosomes change
Forward mutation:

Change away from the wild type
Back mutation (reverse):

Change from mutant to wild type
From DNA to phenotype:
Point Mutation:
Change of one base pair or a small number of
adjacent base pairs
Substitutions: A change in a given base pair

Transition:
category





Purine to purine or pyrimidine to pyrimidine
Adenine (A); Guanine (G) Purine
Cytosine (C), Thymine T) Pyrimidine
Transversion: A replacement of a base of one chemical
category with a base of the other


A replacement within the same chemical
Purine to pyrimidine or pyrimidine to purine
Transitions are more common than transversions
An important distinction in population genetics/systematics
Missense Mutation:
A codon for one amino acid is replaced by another
Synonymous substitution:


Change of an amino acid for a chemically similar one
The affect is less severe
Nonsynonymous substitution:


Change an amino acid for one of different properties
More severe implications
Null mutations:


Non functional mutants
Likely due to changes in the active site (or allosteric)
Leaky (partly inactivated) mutants:

Likely due to changes away from the active site
Nonsense mutations:
A codon for an amino acid is converted
to a stop codon
Typically causes a totally nonfunctional
protein unless it is near the 3' end
Silent Substitutions:
Degenerate DNA codons
Changes to third position in a codon
Does not change the AA
Typically silent...but there are exceptions
Additions/deletions:
Losing or gaining a base pair
Frameshift mutations
Changes the reading fame
Will screw up all of the AAs from the point of the
insertion/deletion
Can extend beyond the protein in question
Typically causes a loss of function mutation
Regulatory Mutations:
Mutations to regulatory binding sites:
Outcome hard to predict
 Does it affect the binding of a regulatory protein?
 If it does how much?
 How many regulators are there?

Mutation to regulatory proteins:
Affect is somewhat more predictable
 However, there are still multiple control systems

Assorted Mutations
Somatic -vs- Germinal
Mutations:
Somatic Mutations:
Mutations in cells outside of the germ line
 The cell becomes the progenitor of a series of
related cells
 These mitotically formed offspring are "clones"
 These cells tend to stay together in the organism
 Form "mutant sectors"
 The earlier the mutation occurs the more
widespread the affects
 Cancer...a special case

Somatic Mutations
Plants:
Can somatic mutations
be passed on?
In animals no
In plants somatic cells
can develop into
germinal cells
Germinal mutation:
Mutations in the germ line
Passed on to the next generation
Assumes the mutant gamete gets into a zygote
"normal" individuals can have "mutant" sex cells
X-linked hemophilia in the royal family
 Started in Queen Victoria's germ line or that of her
parents

Mutation outcomes
Mutant Types:
May be subtle or gross
Morphological mutations: Outwardly visible
Lethal mutations: Are....uh....lethal?
Morphological mutations
Conditional Mutations:
Mutants that only appear in some environments
Restrictive condition:

The environment that causes expression
Permissive condition:

Environment that does not cause expression
Biochemical mutations:
Change in the biochemical function of a cell
Essentially underlies the other categories
The term is often used for microorganisms
Prototrophic:

can survive on a basic medium of salts and an
energy source (minimal medium)
Auxotrophic:

Require an additional nutrient to survive
Biochemical Mutations
Loss/gain of function?
Loss of function mutations:
Gain of function mutations:
Less common than loss
 Why?

Occurrence of mutations:
How common are they?
Organisms are stable generation to generation
Implications?
How common are mutations?
The range is huge

500 fold difference seen in corn genes
Mutation rate:
Mutation rate per unit time
 Typically per generation or per cell division
 1 in 14 generations, 1 in 100 etc.

Mutation frequency:
Frequency of a mutatnt in a population of cells
 Could be single cells, gametes, spores etc.
 Would yield a fractional value
 0.0056 etc.

Frequency of
Mutations
Cancer:
A genetic disease
Due to a somatic mutation
Cancer genes (oncogenes)
Start out as proto-oncogenes
Typically related to regulation of cell division
Proto-oncogenes convert to oncogenes via mutation
Results in uncontrolled cell growth and metastasis
These mutations can be cause spontaneously or by
environmental factors
Proto-oncogenes
Genes in the germ line
Repair mechanisms
Regulation mutations
Mutagens/carcinogens:
Increase the rate of mutation
EM radiation
Chemicals
Cigarettes
Preservative
Herbicides etc. etc.
Mutagens