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