Neutral Theory of Molecular Evolution

1

• Neutral Theory of Molecular Evolution
• most base substitutions are selectively neutral
• drift dominates evolution at the molecular level
• Under drift, rate of fixation should be steady
  through time
• because drift is the result of chance alone (can
  happen any time)
• predicts steady change through time molecular
  clock

ATGGTCAAGCTTACCATG
ATGCTCAAGCTTACCATG
ATGGTCAAGCTTACCATG
ATGGTCAAGATTACCATG
ATGGTCAAGATTACCTTG
ATGGTCAAGATTACCATG
ATGGTCAAGATTACCATC
2

• Challenging the neutral theory
• Are most mutations neutral?
• How does a mutation affects the genes function?
• silent site (synonymous) mutation neutral
• no effect on fitness should drift

ATGGTCAAGCTTACCATG met val lys leu thr met
ATGGTTAAGCTTACCATG met val lys leu thr met
active site
3

• Challenging the neutral theory
• Are most mutations neutral?
• How does a mutation affects the genes function?
• silent site (synonymous) mutation neutral
• no effect on fitness should drift
• replacement site (non-synonymous) mutation not
  always neutral
• how does the mutation affect protein function?
• deleterious ? negative (purifying) selection

ATGGTCAAGCTTACCATG met val lys leu thr met
ATGGTTAAGCTTACCATG met val lys leu thr met
ATGGTCAAGCTTACCATG met val lys leu thr met
ATGGTCACGCTTACCATG met val thr leu thr met
active site
4

• Challenging the neutral theory
• Are most mutations neutral?
• How does a mutation affects the genes function?
• silent site (synonymous) mutation neutral
• no effect on fitness should drift
• replacement site (non-synonymous) mutation not
  always neutral
• how does the mutation affect protein function?
• minimal effect ? drift

ATGGTCAAGCTTACCATG met val lys leu thr met
ATGGTTAAGCTTACCATG met val lys leu thr met
ATGGTCAAGCTTACCATG met val lys leu thr met
ATGGTCACGCTTACCATG met val thr leu thr met
active site
5

• Challenging the neutral theory
• Are most mutations neutral?
• How does a mutation affects the genes function?
• silent site (synonymous) mutation neutral
• no effect on fitness should drift
• replacement site (non-synonymous) mutation not
  always neutral
• how does the mutation affect protein function?
• beneficial effect ? positive selection

ATGGTCAAGCTTACCATG met val lys leu thr met
ATGGTTAAGCTTACCATG met val lys leu thr met
ATGGTCAAGCTTACCATG met val lys leu thr met
ATGGTCACGCTTACCATG met val thr leu thr met
active site
6
Testing the neutral theory

• Where are substitutions (i.e., mutations that
  have become fixed) found?
• What does the neutral theory predict?
• Substitutions equally common at silent sites and
  replacement sites
• What do you predict if negative selection is
  common?
• More substitutions at silent sites
• What do you predict if positive selection is
  common?
• More substitutions at replacement sites
• Studies have detected positive selection in genes
  that code for
• proteins involved in fertilization and disease
  resistance.
• Why would new variations be valuable for these
  proteins???

7

• Speciation
• speciation formation of new species
• How does speciation occur?
• classic hypothesis allopatric speciation
• other hypotheses for how speciation can occur
• How do mutation, migration, selection, drift and
  non-random mating
• affect genetic divergence?

allopatry living in different areas
8
Evolutionary biology since the modern synthesis

• Revising the modern synthesis
• Is evolution always gradual?
• Eldredge and Gould, 1972, Punctuated Equilibrium
• How important is genetic drift relative to
  natural selection?
• Kimura, 1968, Neutral Theory
• Is speciation always slow?
• Does speciation only occur in isolated
  populations?

LECTURE 12
9
Allopatric speciation original hypothesis for
how speciation occurs 3 steps (1)
isolation (geographic)
allopatry living in different areas
population B
species range
population A
geographic isolation
10
Allopatric speciation original hypothesis for
how speciation occurs 3 steps (1)
isolation (geographic) (2) divergence
(mainly by drift)
allopatry living in different areas
population B
population A
geographic isolation
divergence
11
Allopatric speciation original hypothesis for
how speciation occurs 3 steps (1)
isolation (geographic) (2) divergence
(mainly by drift) (3) reproductive isolation
(in secondary contact)
allopatry living in different areas
x
x
x
x
x
x
x
x
x
x
x
population B
x
reproductive isolation
x
x
x
x
x
x
x
x
population A
x
x
x
x
secondary contact
divergence
gene flow
hybrids unfit