1. Time-dependent rates of molecular evolution Evidence and causes Simon Ho School of Biological Sciences

2. Acknowledgements Rob Lanfear, Lindell Bromham, Matt Phillips Australian National University Julien Soubrier, Alan Cooper University of Adelaide Allen Rodrigo Duke University & University of Auckland Jeremy and Barbara 2 Acknowledgements

3. Morphological rates Measured in darwins or haldanes Neontological studies Palaeontological studies Differ by several orders of magnitude 3 Introduction Gingerich (2001)

4. Molecular rates: Pedigrees 4 Introduction Howell et al. (2003)

5. Molecular rates: Phylogenies 5 Introduction 0.06 differenceRate = / 6 Myr = 0.01 / Myr 6 Myr

6. Estimating rates 6 Introduction Fossil recordBiogeographySampling timesPedigrees AB AB Recent split Fast rate Ancient split Slow rate AB

7. Calibration 7 Introduction

8. Evidence 8 Birds (mtDNA) Primates (mtDNA)Primates (D-loop) Ho et al. (2005)

9. Evidence 9 Genner et al. (2007) Burridge et al. (2008)

10. Evidence 10 Evidence Henn et al. (2009) Papadopoulou et al. (2009)

11. Evidence from ancient DNA 11 Evidence

12. Evidence from ancient DNA Evidence 12 Hay et al. (2008)

13. Implications: Human migration 13 Implications Endicott et al. (2009)

14. Implications: Human migration 14 Implications Ho & Endicott (2008)

15. Implications: LPO hypothesis 15 Implications

16. 16 LPO hypothesis Ho et al. (2008)

17. 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 Causes

18. Evidence 18 Biological framework

19. Evidence 19 Biological framework

20. 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 Natural selection Subramanian (2009)

21. Positive selection Selection favouring advantageous mutations Evidence  Adaptive mitochondrial variation in response to climatic factors 21 Natural selection

22. Coalescent calibration error Genetic divergence precedes reproductive isolation 22 Calibration errors Reproductive isolation Genetic divergence

23. Fossil calibration error Fossil appearance is later than genetic divergence 23 Calibration errors 6 Myr

24. Phylogenetic assumptions Mitochondrial DNA  No recombination  Maternally inherited  Homoplasmy 24 Model misspecification

25. Saturation Mutational hotspots Under-correction for saturation over longer time periods 25 Model misspecification

26. Demographic factors Population structure Misspecified demographic model 26 Model misspecification Navascues & Emerson (2009)

27. Sequence error Sequencing error Post-mortem damage (ancient DNA) Artificial mutations  Inflate rate estimates Corrected using phylogenetic models of sequence error 27 Artefacts

28. Ancient DNA Evidence from ancient DNA is pivotal 28 Ancient DNA

29. Heterochronous tips Ages up to 500,000 years 29 Ancient DNA

30. 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 Ancient DNA

31. 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 Concluding remarks