Time-dependent rates of molecular evolution
Evidence and causes
Simon HoSchool of Biological Sciences
Acknowledgements
• Rob Lanfear, Lindell Bromham, Matt PhillipsAustralian National University
• Julien Soubrier, Alan CooperUniversity of Adelaide
• Allen RodrigoDuke University & University of Auckland
• Jeremy and Barbara
2
Ack
now
ledg
emen
ts
Morphological rates
• Measured in darwins or haldanes
• Neontological studies
• Palaeontological studies
• Differ by several orders of magnitude
3
Intro
duct
ion
Gingerich (2001)
Molecular rates: Pedigrees
4
Intro
duct
ion
Howell et al. (2003)
Molecular rates: Phylogenies
5
Intro
duct
ion
0.06 differenceRate = / 6 Myr
= 0.01 / Myr
6 Myr
Estimating rates
6
Intro
duct
ion
Fossil record Biogeography Sampling times Pedigrees
A BA B
Recent splitFast rateAncient split
Slow rate
A B
Calibration
7
Intro
duct
ion
Evidence
8
Evi
denc
e
Birds (mtDNA)
Primates (mtDNA) Primates (D-loop)
Ho et al. (2005)
Evidence
9
Evi
denc
e
Genner et al. (2007)
Burridge et al. (2008)
Evidence
10
Evi
denc
e
Henn et al. (2009)
Papadopoulou et al. (2009)
Evidence from ancient DNA
11
Evi
denc
e
Evidence from ancient DNAE
vide
nce
12Hay et al. (2008)
Implications: Human migration
13
Impl
icat
ions
Endicott et al. (2009)
Implications: Human migration
14
Impl
icat
ions
Ho & Endicott (2008)
Implications: LPO hypothesis
15
Impl
icat
ions
16
LPO hypothesis
Ho et al. (2008)
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
Cau
ses
Evidence
18
Bio
logi
cal f
ram
ewor
k
Evidence
19
Bio
logi
cal f
ram
ewor
k
Negative selection
• Most mutations are deleterious
• Time-dependent decline in ratio of nonsynonymous to synonymous mutations
• Stronger time-dependence of rates in coding DNA
20
Nat
ural
sel
ectio
n
Subramanian (2009)
Positive selection
• Selection favouring advantageous mutations
• Evidence Adaptive mitochondrial variation in response to climatic
factors
21
Nat
ural
sel
ectio
n
Coalescent calibration error
• Genetic divergence precedes reproductive isolation
22
Cal
ibra
tion
erro
rs
Reproductiveisolation
Geneticdivergence
Fossil calibration error
• Fossil appearance is later than genetic divergence
23
Cal
ibra
tion
erro
rs
6 Myr
Phylogenetic assumptions
• Mitochondrial DNA No recombination Maternally inherited Homoplasmy
24
Mod
el m
issp
ecifi
catio
n
Saturation
• Mutational hotspots
• Under-correction for saturation over longer time periods
25
Mod
el m
issp
ecifi
catio
n
Demographic factors
• Population structure
• Misspecified demographic model
26
Mod
el m
issp
ecifi
catio
n
Navascues & Emerson (2009)
Sequence error
• Sequencing error
• Post-mortem damage(ancient DNA)
• Artificial mutations Inflate rate estimates
• Corrected usingphylogenetic modelsof sequence error
27
Arte
fact
s
Ancient DNA
• Evidence from ancient DNA is pivotal
28
Anc
ient
DN
A
Ancient DNA
• Heterochronous tips
• Ages up to 500,000 years
29
Anc
ient
DN
A
Challenges
• 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
Anc
ient
DN
A
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
Con
clud
ing
rem
arks