Time-dependent rates of
molecular evolution
Evidence and causes
Simon Ho
School of Biological Sciences
Acknowledgements
•
Rob Lanfear, Lindell Bromham, Matt Phillips
Acknowledgements
Australian National University
•
Julien Soubrier, Alan Cooper
University of Adelaide
•
Allen Rodrigo
Duke University & University of Auckland
•
Jeremy and Barbara
2
Introduction
Morphological rates
•
Measured in
darwins or
haldanes
•
Neontological
studies
•
Palaeontological
studies
•
Differ by several
orders of
magnitude
Gingerich (2001)
3
Introduction
Molecular rates: Pedigrees
Howell et al. (2003)
4
Introduction
Molecular rates: Phylogenies
6 Myr
Rate = 0.06 difference / 6 Myr
= 0.01 / Myr
5
Estimating rates
A
A
B
A
B
B
Recent split
Fast rate
Introduction
Ancient split
Slow rate
Fossil record
Biogeography
Sampling times
Pedigrees
6
Introduction
Calibration
7
Evidence
Evidence
Birds (mtDNA)
Primates (mtDNA)
Primates (D-loop)
Ho et al. (2005)
8
Evidence
Evidence
Genner et al. (2007)
Burridge et al. (2008)
9
Evidence
Evidence
Henn et al. (2009)
Papadopoulou et al. (2009)
10
Evidence
Evidence from ancient DNA
11
Evidence
Evidence from ancient DNA
Hay et al. (2008)
12
Implications
Implications: Human migration
Endicott et al. (2009)
13
Implications
Implications: Human migration
Ho & Endicott (2008)
14
Implications
Implications: LPO hypothesis
15
LPO hypothesis
Ho et al. (2008)
16
Causes
Causes
•
The basic biological framework
•
The effects of natural selection
•
The effects of calibration errors
•
The effect of model misspecification
•
Artefacts causing time-dependent molecular rates
17
Biological framework
Evidence
18
Biological framework
Evidence
19
Negative selection
Natural selection
•
Most mutations are deleterious
•
Time-dependent decline in ratio of nonsynonymous to
synonymous mutations
•
Stronger time-dependence of rates in coding DNA
Subramanian (2009)
20
Natural selection
Positive selection
•
Selection favouring advantageous mutations
•
Evidence

Adaptive mitochondrial variation in response to climatic
factors
21
Coalescent calibration error
Calibration errors
•
Genetic divergence precedes reproductive isolation
Reproductive
isolation
Genetic
divergence
22
Fossil calibration error
Fossil appearance is later than genetic divergence
Calibration errors
•
6 Myr
23
Phylogenetic assumptions
Model misspecification
•
Mitochondrial DNA

No recombination

Maternally inherited

Homoplasmy
24
Model misspecification
Saturation
•
Mutational hotspots
•
Under-correction for saturation over longer time periods
25
Model misspecification
Demographic factors
•
Population structure
•
Misspecified demographic model
Navascues & Emerson (2009)
26
Artefacts
Sequence error
•
Sequencing error
•
Post-mortem damage
(ancient DNA)
•
Artificial mutations

•
Inflate rate estimates
Corrected using
phylogenetic models
of sequence error
27
Ancient DNA
Evidence from ancient DNA is pivotal
Ancient DNA
•
28
Ancient DNA
Heterochronous tips
•
Ages up to 500,000 years
Ancient DNA
•
29
Challenges
Ancient DNA
•
Ancient DNA data from populations

Low variation

Small range of sampling times

Lack of control over sampling design

Cost of radiocarbon dating

Post-mortem damage
30
Concluding remarks
Concluding remarks
•
Difficulties in estimating rates empirically
•
Paucity of reliable age calibrations
•
Range of potential biological and methodological
causes
•
We need to disentangle
these factors so that we
can estimate timescales
accurately
31