1. Lecture 24: Human Origins and Signatures of Selection April 11, 2014

2. Announcements  Switched labs 11 and 12  Phylogenetics and Coalescence this week (lab 12 in the manual)  Signatures of selection next week (lab 11 in the manual)

3. Last Time uGene trees versus species trees uCoalescence uInfluence of demographic factors on coalescence times

4. Today uHuman origins: Neanderthals and Denisovans uSignatures of selection

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

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

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

8. Origin of modern humans Models of Human Origin Garrigan and Hammer 2006 Nature Reviews Genetics 7:669

9. Human Evolutionary History http://www.cartage.org.lb/en/themes/sciences/paleontology/paleozoology/fossilhominids/ChartHumanEvolution/ChartHumanEvolution.htm

10. Neanderthals  Occurred in Europe and central Asia from 400,000 to 30,000 ybp  Morphological features distinguished them from modern humans:  strongly-built, stocky frame  long, low skull with large cranial capacity  Double-arched brow ridges  occipital ‘bun’  large nose, big front teeth  Disappeared from fossil record shortly after Homo sapiens appeared in Europe http://www.msnbc.msn.com Nature 465:148, 2010

11. What happened to the Neanderthals?  Extinction with no genetic legacy?  Do Neanderthals live on within our own genomes?  Neanderthal genome sequences are now answering those questions! http://www.isayev.info

12. Archaic Genomics - Svante Pääbo March 27, 2014, NIH https://www.youtube.com/watch?v=M7VdRKQuAa8

13. Neanderthal Mitochondrial Sequence  DNA extracted from bone fragments from 4 locations  Sequenced using Next-Gen technology: Roche 454 FLX  One individual (from Croatia) sequenced to great depth to give reference genome Briggs et al. 2009 Science 325:318

14. Neanderthal and Human Mitochondrial Tree  Neanderthals and humans show no evidence of admixture  Most ancient Neanderthals (easternmost) are also most differentiated  Very low population structure and low diversity in most recent Neanderthals  Low effective population size? Bottleneck? Stay tuned. https://www.youtube.com/watch?v=M7VdRKQuAa8

15. Neanderthal “Complete” Genome Sequence  DNA extracted from bone fragments from Vindijia Cave, Croatia  95-99% of DNA was from microbes  Cut DNA with restriction enzymes with high CpG recognition sites: eliminate bacterial DNA  Sequenced with 454 and Illumina GAII  5.3 Gb of sequence produced Green et al. 2010 Science 328: 710

16. Human-Neanderthal Hybridization Green et al. 2010 Science 328: 710 uSegments in European human genome with high identity to Neanderthals are very different from other human sequences uNot true for African sequences uEvidence for hybridization with Europeans, not Africans Distance from Neanderthal Distance from Modern Humans

17. Human-Neanderthal Hybridization uFour possible scenarios for hybridization uScenario 3 most likely: hybridization with ancestor of all modern Asian and European lineages after splitting from Africa Green et al. 2010 Science 328: 710

18. Mithochondrial and Nuclear Stories are Different https://www.youtube.com/watch?v=M7VdRKQuAa8

19. Why would mitochondrial DNA give a different answer than nuclear DNA? What other questions could be addressed with ancient, introgressed DNA?

20. https://www.youtube.com/watch?v=M7VdRKQuAa8

29. Expectations for Hybridization

34. Do Ancient Humans Show Larger Chromosome Segments from Neanderthals than Modern Humans?

36. 45,000 year old human fossil genome

37. More admixture in 45,000 year old human (and Asians)

38. A new human ancestor: Denisovans

39. http://www.time.com/time/health/article/0,8 599,1974903,00.html uSingle finger bone and some teeth discovered in cave in Siberia uFound in conjunction with human-like artifacts: bracelets and necklaces uSequenced mitochondrion and whole genome (1.9X) using Illumina GAII uDNA sequence reveals this is not a human bone!

40. Denisovans are closer to Neanderthals, but very different Neanderthals Modern Humans

42. Eurasians Probably had continued introgression from other hominids after divergence from Africans

43. Patterns of Introgression in Modern Humans and Relatives

45. Summary https://www.youtube.com/watch?feature=pla yer_detailpage&v=M7VdRKQuAa8#t=1661 https://www.youtube.com/watch?feature=pla yer_detailpage&v=M7VdRKQuAa8#t=1661 \

46. Are Neanderthal and Denisovan Genome Remnants Adaptive?

47. The main power of neutral theory is it provides a theoretical expectation for genetic variation in the absence of selection.

48. Assume you take a sample of 100 alleles from a large (but finite) population in mutation-drift equilibrium. A. Number of Observations of Allele Number of Alleles 2 4 6 8 10 2468 B. 246810 C. 246810 What is the expected distribution of allele frequencies in your sample under neutrality and the Infinite Alleles Model?