1. Human Chimp How does DNA evolve? Nucleotide substitutions
1 ATGCCCCAACTAAATACTACCGTATGGCCCACCATAATTACCCCCATACT 50
||||||||||||||||| ||||||| |||||||||||||||||||||||
1 atgccccaactaaataccgccgtatgacccaccataattacccccatact 50
51 CCTTACACTATTCCTCATCACCCAACTAAAAATATTAAACACAAACTACC 100
||| |||||||| ||| |||||||||||||||||||||| |||| ||||
51 cctgacactatttctcgtcacccaactaaaaatattaaattcaaattacc 100
101 ACCTACCTCCCTCACCAAAGCCCATAAAAATAAAAAATTATAACAAACCC 150
| ||||| ||||||||||| ||||||||||||||||| || || ||||||
101 atctacccccctcaccaaaacccataaaaataaaaaactacaataaaccc 150
151 TGAGAACCAAAATGAACGAAAATCTGTTCGCTTCATTCATTGCCCCCACA 200
||||||||||||||||||||||||| |||||||||||| ||||||||||
151 tgagaaccaaaatgaacgaaaatctattcgcttcattcgctgcccccaca 200
201 ATCC 204
||||
201 atcc 204

2. New mutations = 2N x u
Probability of a new mutation fixing = 1/2N
Rate of NEUTRAL Evolution = 2Nu x 1/2N = u

3. Measuring DNA Evolution
Align sequences
Determine length of sequences
Count number of differences
Divergence =
(number of differences) / (length of sequence)
Divergence Rate =
(sequence divergence) / (age of common ancestor)
Substitution Rate =
(sequence divergence) / (2Xage of common ancestor)
D. melanogaster vs. D. simulans
3 diffs.
D= =0.043
70 amino acids
Rate of divergence = = 1.74 x 10-8 amino acid differences per year
2.5 million years
Substitution rate = half of that on each lineage (5 million TOTAL years of divergence)

4. Fixed differences vs. Polymorphisms• • • • -t
MRCA
-tw
0 = present
Origination
Fixation
Site
Frequency

5. • approximately linear sequence divergence over time
Molecular clocks:
• approximately linear sequence divergence over time
• different genes have different functional constraints
• this causes different rates of evolution
• different nucleotide positions evolve at different rates

6. Molecular clocks and the neutral theory
Substitution of new allele
AA Aa aa
1 1+s 1+2s
Requires elimination of old allele
Lots of genetic deaths
Rates of molecular evolution are too fast to be explained by positive selection
Too much genetic load
Substitution load
Load = (Woptimal - Wbar) / Woptimal
Kimura: The majority of substitutions at the molecular level are neutral in evolution
Different proteins evolve at different rates due to different levels of functional constraint •
Observation: molecular clocks
are approximately linear • • •
Fibrino
peptides • •
Percent
sequence
divergence • • •
Hemo
globin • • • • • • • • • • • • •
Cytochrome c •
Date of divergence
(millions of years)

7. Mutation drift equilibrium

9. Living fossils slow rates of morphological change
Coelocanth
Only living crossopterygian
Thought to be extinct; caught in a net off Africa
Horseshoe crab
No obvious morphological change for ~150 million years
Birds evolved
Dinosaurs rose and went extinct
Mammals , land plants diversified
Horseshoe crab stasis due to life in relatively stable near-shore environment?

10. Tempo and Mode
Of Evolution:
Horseshoe ‘crabs’
and hermit crabs:
Similar rates of
molecular evolution
different rates of
morphological
evolution

11. What defines a neutral mutation? Answer: When s < 1/2Ne
Observation:
Rates of molecular evolution are surprisingly constant in different species
Puzzle:
Why don’t species with short generation time have faster evolution?
What defines a neutral mutation?
Answer: When s < 1/2Ne
Short generation time:
Many mutations
Few are neutral (Ne is large)
Long generation time:
Few mutations
Many are neutral (Ne is small)

12. Protein polymorphism and the neutral theory
Observation from allozyme data:
About 1/4 of loci are polymorphic
About 3000 loci in fruitflies
Heterozygosity ~ 0.3 on average
Is variation maintained by selection?
AA Aa aa
1-s 1 1-t
This requires lots of genetic deaths
Homozygotes eliminated
Genetic load
Segregation load
Load = (Woptimal - Wbar) / Woptimal
For 3000 loci with 10% selection (s and t = 5% each) this load could be huge
Too much genetic death to allow balancing selection
No problem if alleles are neutral
No genetic load with neutrality
SS SF FF SF FF SS SF SF
well
bands
Geno
types
SS SF FF SF SS SF FF SF
Monomorphic
enzyme
Dimeric
Kimura and Ohta:
Protein polymorphism as a phase
Of neutral evolution