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

2Ack

now

ledg

emen

ts

Morphological rates

• Measured in darwins or haldanes

• Neontological studies

• Palaeontological studies

• Differ by several orders of magnitude

3Intr

oduc

tion

Gingerich (2001)

Molecular rates: Pedigrees

4Intr

oduc

tion

Howell et al. (2003)

Molecular rates: Phylogenies

5Intr

oduc

tion 0.06 differenceRate = / 6 Myr

= 0.01 / Myr

6 Myr

Estimating rates

6Intr

oduc

tion

Fossil record Biogeography Sampling times Pedigrees

A BA B

Recent splitFast rateAncient split

Slow rate

A B

Calibration

7Intr

oduc

tion

Evidence

8Evi

denc

e

Birds (mtDNA)

Primates (mtDNA) Primates (D-loop)

Ho et al. (2005)

Evidence

9Evi

denc

e

Genner et al. (2007)

Burridge et al. (2008)

Evidence

10Evi

denc

e Henn et al. (2009)

Papadopoulou et al. (2009)

Evidence from ancient DNA

11Evi

denc

e

Evidence from ancient DNAE

vide

nce

12Hay et al. (2008)

Implications: Human migration

13Impl

icat

ions

Endicott et al. (2009)

Implications: Human migration

14Impl

icat

ions

Ho & Endicott (2008)

Implications: LPO hypothesis

15Impl

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

17Cau

ses

Evidence

18Bio

logi

cal f

ram

ewor

k

Evidence

19Bio

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

20Nat

ural

sel

ectio

n

Subramanian (2009)

Positive selection

• Selection favouring advantageous mutations

• Evidence Adaptive mitochondrial variation in response to climatic

factors

21Nat

ural

sel

ectio

n

Coalescent calibration error

• Genetic divergence precedes reproductive isolation

22Cal

ibra

tion

erro

rs Reproductiveisolation

Geneticdivergence

Fossil calibration error

• Fossil appearance is later than genetic divergence

23Cal

ibra

tion

erro

rs

6 Myr

Phylogenetic assumptions

• Mitochondrial DNA No recombination Maternally inherited Homoplasmy

24Mod

el m

issp

ecifi

catio

n

Saturation

• Mutational hotspots

• Under-correction for saturation over longer time periods

25Mod

el m

issp

ecifi

catio

n

Demographic factors

• Population structure

• Misspecified demographic model

26Mod

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

27Art

efac

ts

Ancient DNA

• Evidence from ancient DNA is pivotal

28Anc

ient

DN

A

Ancient DNA

• Heterochronous tips

• Ages up to 500,000 years

29Anc

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

30Anc

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

31Con

clud

ing

rem

arks