1. Lecture 23: Introduction to Coalescence April 7, 2014

2. Last Time uIntroduction to phylogenetics uPhylogeography uLimitations of phylogenetic analysis

3. Today uGene trees versus species trees uCoalescence uInfluence of demographic factors on coalescence times uCoalescence and human origins

4. Gene Trees vs Species Trees  Genes (or loci) evolve at different rates  Why?  Topology derived by a single gene may not match topology based on whole genome, or morphological traits ACB Gene Tree

5. Coalescence  Retrospective tracing of existing alleles to a common ancestral allele  A reverse reconstruction of the evolution of modern variation  Allows explicit simulation of sequence evolution  Incorporation of factors that cause deviation from neutrality: selection, drift, and gene flow

6. present Time Individual alleles

7. abc Concordant Gene Tree b is closer to a than to c Failure to coalesce within species lineages drives divergence of relationships between gene and species trees Gene Trees vs Species Trees abc Divergent Gene Tree: b is closer to c than to a

8. How to model this process?

9. Modeling from Theoretical Ancestors: Forward Evolution uCan model populations in a forward direction, starting with theoretical past uFisher-Wright model of neutral evolution uVery computationally intensive for large populations

10. Alternative: Start at the end and work your way back present Most recent common ancestor (MRCA) Time Individual alleles Slide courtesy of Yoav Gilad

11. present Most recent common ancestor (MRCA) The genealogy of a sample of 5 gene copies Time individuals Slide courtesy of Yoav Gilad

12. present Most recent common ancestor (MRCA) The genealogy of a sample of 5 gene copies Time Individual alleles Slide courtesy of Yoav Gilad

13. Examples of coalescent trees for a sample of 6 Time Individual alleles Slide courtesy of Yoav Gilad

14. Coalescence Advantages  Don’t have to model dead ends  Only consider lineages that survive to modern day: computationally efficient  Based on actual observations  Can simulate different evolutionary scenarios to see what best fits the observed data

15. Coalescent Tree Example  Coalescence: Merging of two lineages in the Most Recent Common Ancestor (MRCA)  Waiting Time: time to coalescence for two lineages  Increases with each coalescent event

16. Probability of Coalescence  For any two lineages, function of population size  Also a function of number of lineages where k is number of lineages

17. Probability of Coalescence  Probability declines over time  Lineages decrease in number  Can be estimated based on negative exponential where k is number of lineages

18. Time to Coalescence Affected by Population History Bottleneck

19. Time to Coalescence Affected by Population History Population Growth

20. How will population structure affect coalescence times?

21. Time to Coalescence Affected by Population Structure

22. Applications of the Coalescent Approach  Framework for efficiently testing alternative models for evolution  Inferences about effective population size  Detection of population structure  Signatures of selection (coming attraction)  Reconstructing history of populations

23. Origins of Modern Humans uMost fossil evidence points to origins in Africa and subsequent migrations http://www.dhushara.com/book/unraveltree/unravel.htm Skulls found in Omo Valley, Ethiopia Dated at ~195K http://www- v1.amnh.org/exhibitions/ permanent/humanorigins /history/origin.php Omo 1 Modern

24. Human Phylogeography: mtDNA uMost ancient and diverse haplotypes in Africa (dots) uMigration and admixture is evident from presence of African haplotypes in other clades

25. Complexities to Human Phylogeography uSome genes show evidence of Asian origin  Sequence of X-linked ribonucleotide reductase M2 pseudogene 4 (RRM2P4) Garrigan 2007 Nature Reviews Genetics 7:669

26. Why might some X-linked genes show a human origin in Africa (e.g., PDHA1), while others suggest an Asian origin e.g., (RRM2P4)?

27. Evidence of Population Structure in Ancient Humans Garrigan and Hammer 2006 Nature Reviews Genetics 7:669

28. Time to Coalescence Affected by Population Structure

29. Evidence for Ancient Population Structure in Nuclear but not Mitochondrial Trees Garrigan and Hammer 2006 Nature Reviews Genetics 7:669

30. Why does mitochondrion show shorter coalescence times than nuclear loci? Why does rate vary much more for nuclear loci?