Biology 331: Chapter 15

1
Biology 331 Chapter 15

• Gene Mutation

2
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

3
From DNA to phenotype
4
Point Mutation

• Change of one base pair or a small number of
  adjacent base pairs
• Substitutions A change in a given base pair
• Transition A replacement within the same
  chemical 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
• Purine to pyrimidine or pyrimidine to purine
• Transitions are more common than transversions
• An important distinction in population
  genetics/systematics

5
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

6
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

7
Silent Substitutions

• Degenerate DNA codons
• Changes to third position in a codon
• Does not change the AA
• Typically silent...but there are exceptions

8
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

9
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

10
Assorted Mutations
11
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

12
Somatic Mutations
13
Plants

• Can somatic mutations be passed on?
• In animals no
• In plants somatic cells can develop into germinal
  cells

14
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

15
Mutation outcomes
16
Mutant Types

• May be subtle or gross
• Morphological mutations Outwardly visible
• Lethal mutations Are....uh....lethal?

17
Morphological mutations
18
Conditional Mutations

• Mutants that only appear in some environments
• Restrictive condition
• The environment that causes expression
• Permissive condition
• Environment that does not cause expression

19
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

20
Biochemical Mutations
21
Loss/gain of function?

• Loss of function mutations
• Gain of function mutations
• Less common than loss
• Why?

22
Occurrence of mutations

• How common are they?
• Organisms are stable generation to generation
• Implications?

23
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.

24
Frequency of Mutations
25
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

26
Proto-oncogenes
27
Genes in the germ line

• Repair mechanisms
• Regulation mutations

28
Mutagens/carcinogens

• Increase the rate of mutation
• EM radiation
• Chemicals
• Cigarettes
• Preservative
• Herbicides etc. etc.

29
Mutagens