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Lecture 24 : Human Origins and Signatures of Selection

Lecture 24 : Human Origins and Signatures of Selection. April 11, 2014. 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). Last Time. Gene trees versus species trees Coalescence

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Lecture 24 : Human Origins and Signatures of Selection

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  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 • Gene trees versus species trees • Coalescence • Influence of demographic factors on coalescence times

  4. Today • Human origins: Neanderthals and Denisovans • Signatures 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. Models of Human Origin Origin of modern humans 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 Nature 465:148, 2010 http://www.msnbc.msn.com

  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 Distance from Modern Humans Distance from Neanderthal • Segments in European human genome with high identity to Neanderthals are very different from other human sequences • Not true for African sequences • Evidence for hybridization with Europeans, not Africans Green et al. 2010 Science 328: 710

  17. Human-Neanderthal Hybridization • Four possible scenarios for hybridization • Scenario 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

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

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

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

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

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

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

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

  28. Expectations for Hybridization

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

  30. 45,000 year old human fossil genome

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

  32. A new human ancestor: Denisovans

  33. A new human ancestor: Denisovans • Single finger bone and some teeth discovered in cave in Siberia • Found in conjunction with human-like artifacts: bracelets and necklaces • Sequenced mitochondrion and whole genome (1.9X) using Illumina GAII • DNA sequence reveals this is not a human bone! http://www.time.com/time/health/article/0,8599,1974903,00.html

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

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

  36. Patterns of Introgression in Modern Humans and Relatives

  37. Summary • https://www.youtube.com/watch?feature=player_detailpage&v=M7VdRKQuAa8#t=1661 • \

  38. Are Neanderthal and Denisovan Genome Remnants Adaptive?

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

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

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