Is heterozygosity common or rare? Sewell Wright Theodosius Dobzhansky.
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Transcript of Is heterozygosity common or rare? Sewell Wright Theodosius Dobzhansky.
Is heterozygosity common or rare?
Sewell Wright
Theodosius Dobzhansky
Neutral Theory
“The vast majority of substitutions in DNA and
proteins, and polymorphism within species, are caused not
by positive Darwinian selection, but by random drift of alleles that are selectively
neutral or neearly so.”
Neutral Theory of Molecular Evolution
1) For each protein, the rate of evolution (amino acid substitution) is approximately constant per generation as long as the functional constraint (fo, fraction of neutral mutations) remains constant
2) Functionally less important molecules or parts thereof will have a higher substitution rate than functionally important ones
3) Those substitutions that disrupt proteins less will occur more frequently than those that disrupt more
4) Selective elimination of alleles and the random fixation of neutral alleles are more prevalent than alleles fixed by positive Darwinian selection
5) Polymorphism is a transient phase of molecular evolution (substitution), not an adaptive stable state. Constant input of mutations, not natural selection, is the cause of polymorphism.
Justification for neutral theory
Kimura, M. 1968. Nature 217: 624-6.
Endorsement of the Neutral Theory
Science (1969) 164: 788-798
Critiques of the Neutral Theory
Inconsistencies with the neutral theory
• Overdispersion of the protein clock
• Lack of a generation time effect in protein clock
• Heterozygosity is much lower, and more even among species, than predicted from population size.
Calibrating a molecular clock is like estimating the speed of a car
2 present-day species
Fossil species suspected to be the commonancestor of A and B
A B
Time (millions of years)
Rate = number of genetic differences twice the divergence time of A and B
geneticdifferences
Single calibration point - a no-noin modern rate analyses
Fossil calibrations of turtle phylogeny
Hominid slowdown
Males in the fast lane
• 56• 57• 91-205
• 27• 28• 33
The larger number of cell divisions undergone by sperm during gametogenesis predicts that the Y chromosome of mammals (or the
Z chromosome of birds) should change faster than the X (or W) chromosome.
Males FemalesSpecies
Number of germ line divisions
MiceMice RatsRats HumansHumans
M:F Ratio
2.12.1 2.02.0 3-63-6
Body size and rate of molecular evolution
The link between metabolic rate and molecular change
(Martin and Palumbi 1993; Bleiweiss 1998)
Metabolic rate
Oxidative damage
Rate of mutation
Large mammals
Small mammals
High altitudehummingbirds
Low altitudehummingbirds
Who’s fastest among the birds and beasts?
• Rodents
• Primates
• Birds
• Fish
• Short generation times; high metabolic rates
• Longer generation times
• Higher body temperatures, good 02 scavengers
• Ectotherms; often cold environments
Faster clock
Copyright ©2004 by the National Academy of Sciences
Cho, Yangrae et al. (2004) Proc. Natl. Acad. Sci. USA 101, 17741-17746
Fig. 1. Substitution rates in Plantago are highly elevated and variable in mt genes compared with chloroplast (cp) and nuclear (nc) genes
Phe 12s rRNAVal
16s rRNA
LeuIle
Gln
Met
Trp
Ala
Asn
Cys
Tyr
COI
SerAspCOII
LysATP8
ATP6COIII
GlyNADH3
Arg
NADH4L
NADH4
His
Ser
Leu
NADH5
Cyt b
Thr
Control Region
Pro
NADH6
Glu
noncoding
Fast rate of vertebrate mitochondrial DNA (~17,000 bp)
rRNA genes
tRNA genes
ATP synthase genes
Cytochrome bc1 complex
Cytochrome Oxidase
NADH:Ubiquinone Oxidoreductase
NADH1
NADH2
Rate acceleration in FOXP2, a ‘speech’ gene in humans
Recent controversies involving molecular clocks
• Divergence time of humans and chimps
• Origin of modern humans
• Origin of animals and the Cambrian explosion
• Origin of birds and mammals
• 15 million years ago
• 1 million years ago
• 600 million years ago
• 60 million years ago
Controversy Old divergence time New divergence time
5 million years ago 5 million years ago
200,000 years ago200,000 years ago
1.2 billion years 1.2 billion years agoago
110 million years 110 million years agoago
Nearly Neutral Theory(Tomoko Ohta)
• Recognizes that mutations in which 2Ns << 1 behave as if they are neutral, even if deleterious or advantageous.
Small population large population
Fixation probability of nearly neutral mutations
Fixation probability
Comparison of neutral and nearly neutral world views
Distribution of fitness effects of spontaneous mutations
Distribution of fitness effects of spontaneous mutations
Speciation and the rate of molecular evolution
Neutral theory: E = M x F: Surprisingly, bottlenecks have noinfluence on the rate at which neutral variation is incorporated (fixed)
into new species; only changes in mutation rate can ultimately change E. However, for non-neutral variation, bottlenecks can accelerate or retard change
population bottlenecks
neutral
non-neutral
Rat
e of
mol
ecul
ar
evol
utio
n
Tests of nearly neutral theory using island birds
Synonymous Non-synonymous