Bio380 Human Evolution: Waking the dead


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Bio380 Human Evolution, genes and genomes lecture on contribution of archaic populations to gene pool of anatomically modern humans, including Neanderthals and Denisovan

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Bio380 Human Evolution: Waking the dead

  1. 2. Bio380: Waking the Dead Neanderthal genes and genomes Professor Mark Pallen
  2. 3. Bio380 Genes and Genomes lectures <ul><li>Lecture 1 Waking the Dead </li></ul><ul><li>Lecture 2 Scatterlings of Africa </li></ul><ul><li>Lecture 3 Major Population Movements: Peopling of the World </li></ul><ul><li>Lecture 4 The Wandering Gene </li></ul><ul><li>Lecture 5 The Phylogenomics of Cancer </li></ul><ul><li>Open Education </li></ul><ul><ul><li>all lectures on YouTube and Slideshare </li></ul></ul><ul><ul><li>Facebook Bio380 site </li></ul></ul><ul><ul><li>Twitter feed #Bio380 </li></ul></ul>
  3. 4. Learning outcomes <ul><li>At the end of this lecture you should be able to answer these questions: </li></ul><ul><ul><li>who were the Neanderthals? </li></ul></ul><ul><ul><li>what is their relationship to us? </li></ul></ul><ul><li>On this issue, you will be able to evaluate </li></ul><ul><ul><li>evidence from genes </li></ul></ul><ul><ul><li>evidence from genomes </li></ul></ul><ul><li>You will be able to describe the contribution of other archaic hominins to the modern human gene pool </li></ul>
  4. 5. Neandert(h)al <ul><li>Valley near Düsseldorf </li></ul><ul><li>Named after 17th century pastor, Joachim Neumann </li></ul><ul><li>Thal became Tal in 1901 </li></ul><ul><ul><li>But old form still used in taxonomy </li></ul></ul><ul><ul><li>And annoyingly both forms common in papers! </li></ul></ul>
  5. 6. Discovery <ul><li>Numerous caves and rock shelters along valley, including Kleine Feldhof Grotte </li></ul><ul><li>In 1850s, limestone quarrying began by firm of Beckershoff and Pieper; caves and valley walls removed </li></ul><ul><li>August 1856, skull cap and 15 postcranial bones recovered from Kleine Feldhof Grotte </li></ul><ul><ul><li>first thought to be cave bear </li></ul></ul><ul><ul><li>shown to local teacher and natural historian Fuhlrott, who identified them as human </li></ul></ul><ul><ul><li>first reported scientifically by Fuhlrott and Schaaffhausen in 1857 </li></ul></ul><ul><li>Neanderthal 1 became type specimen for Homo neanderthalensis </li></ul><ul><li>“ prequals”; Gibraltar 1848, Engis, Belgium, 1829 </li></ul>
  6. 7. Discovery <ul><li>Neanderthal 1 became type specimen for Homo neanderthalensis </li></ul><ul><li>“ prequals” </li></ul><ul><ul><li>Gibraltar 1848 </li></ul></ul><ul><ul><li>Engis, Belgium, 1829 </li></ul></ul><ul><li>Darwin Sept 1864 letter to his close friend, botanist Joseph Hooker: “F[alconer] brought me the wonderful Gibraltar skull.” </li></ul>
  7. 8. Re-discovery...
  8. 9. >400 specimens found
  9. 12. Timeline <ul><li>First proto-Neanderthal features ~350Kya </li></ul><ul><li>Full-blown Neanderthals: </li></ul><ul><ul><li>130Kya-30Kya </li></ul></ul><ul><ul><li>died out by 50Kya in Asia </li></ul></ul><ul><ul><li>?survived to 24Kya in Europe </li></ul></ul><ul><li>Overlapped in time and range with AMH </li></ul><ul><ul><li>but no overlap at any one site </li></ul></ul>
  10. 13. Culture <ul><li>Mousterian culture </li></ul><ul><ul><li>tool use, fire, burials, skinning </li></ul></ul><ul><ul><li>cared for their injuried </li></ul></ul><ul><li>? Language: hyoid bone found in 1983 </li></ul><ul><li>Carnivores (evidence from isotopic studies) </li></ul><ul><ul><li>cannibals? ritual defleshing </li></ul></ul>
  11. 14. Anatomically distinct from AMH <ul><li>differences > than in 2 chimp species </li></ul><ul><li>more robust than AMH </li></ul><ul><li>pronounced brow ridge </li></ul><ul><li>projecting mid-face </li></ul><ul><li>low flat elongated skull; occipital bun </li></ul><ul><li>chinless with larger brains!? </li></ul>
  12. 15. Fate of the Neanderthals <ul><li>Coexistence for 15-20 ky </li></ul><ul><li>Possible fates </li></ul><ul><ul><li>Rapid extinction (genocide) </li></ul></ul><ul><ul><li>Gradual extinction </li></ul></ul><ul><ul><ul><li>unable to adapt to end of glaciation </li></ul></ul></ul><ul><ul><ul><li>cannot compete with humans, e.g. in hunting, running </li></ul></ul></ul><ul><ul><li>Assimilation </li></ul></ul>
  13. 17. Was their genetic exchange between AMH and Neanderthals? OR Africa Eurasia Africa Eurasia Neanderthals Neanderthals
  14. 18. What can sequences tell us <ul><li>Population genetics of modern populations </li></ul><ul><ul><li>Are there sequences in Europeans not found elsewhere old enough to be Neanderthal in origin? </li></ul></ul><ul><ul><li>Torroni et al 1994 and Richards et al 1996 say no </li></ul></ul><ul><li>Ancient DNA </li></ul><ul><ul><li>What do Neanderthal sequences look like? </li></ul></ul><ul><ul><li>Relies on amplification or retrieval of sequences from fossils </li></ul></ul><ul><ul><li>Problem of contamination with human DNA </li></ul></ul>
  15. 19. Mitochondrial DNA <ul><li>favoured because </li></ul><ul><ul><li>100-10,000 copies per cell </li></ul></ul><ul><ul><li>D-loop non-coding </li></ul></ul><ul><ul><li>Maternal transmission </li></ul></ul>
  16. 20. Neanderthal sequence outside modern human range
  17. 25. Summary of Evidence from mtDNA <ul><li>Neanderthal mtDNA is quite different from </li></ul><ul><ul><li>all present human mtDNA sequences </li></ul></ul><ul><ul><li>ancient mtDNA sequences from AMHs </li></ul></ul><ul><li>Common interpretations </li></ul><ul><ul><li>two separate species </li></ul></ul><ul><ul><li>little or no admixture </li></ul></ul><ul><ul><li>consistent with out-of-Africa hypothesis </li></ul></ul>
  18. 26. November 2006…
  19. 28. The verdict...
  20. 30. “ By contrast, the complete Neandertal mtDNA now offers 133 such positions. This enables a reliable estimation of mtDNA contamination by analyzing sequence reads from 454 libraries, rather than by PCR-based assays of the DNA extracts. For example, when we do this in a small preliminary data set initially published from this fossil (Green et al., 2006), 10 of 10 sequences are classified as Neandertal. However, in further unpublished sequencing runs from that library, 8 out of 75 diagnostic sequences derive from extant human mtDNA, suggesting a contamination rate of 11% (CI = 4.7%–20%). This is in agreement with the suggestion (Wall and Kim, 2007) that contamination occurred in that experiment .”
  21. 32. Darwin’s 200 th Birthday February 12 th 2009 <ul><li>1X draft sequence of Neanderthal genome announced </li></ul><ul><ul><li>~60% of genome </li></ul></ul><ul><ul><li>Sequenced 68.9 billion bases, 96% of which were microbial in origin, to cull 3 billion bases of 1X Neanderthal genome </li></ul></ul><ul><ul><li>Three bone fragments from two Neanderthal women: no Y chromosome sequences </li></ul></ul><ul><li>1000-2000 amino acid differences from AMH (cf 50,000 in chimp) </li></ul><ul><ul><li>No evidence of admixture </li></ul></ul><ul><ul><li>No evidence of recently emerging non-African Microcephalin or MAPT variants </li></ul></ul><ul><li>Divergence date ~800Ka </li></ul><ul><li>Formal publication awaited! </li></ul>
  22. 34. Neanderthal genome <ul><li>Comparisons with chimp and AMH genomes found 78 base substitutions that change protein sequences in AMH lineage; 5 proteins with >1 amino-acid change </li></ul><ul><ul><li>SPAG17 (axoneme protein); PCD16 (fibroblast cadherin); TTF1 (transcription termination factor); CAN15 (unknown); RPTN (reptin, skin ECM protein) </li></ul></ul><ul><ul><li>Copy number changes, e.g. PRR20 68 copies in Neanderthal; 18 in AMH </li></ul></ul>
  23. 35. Selective sweeps
  24. 36. Selective sweeps <ul><li>Neanderthals fall within variation in modern humans in many parts of genome </li></ul><ul><li>Allows search for regions subject to selective sweeps in AMH </li></ul><ul><li>Gene affected include: </li></ul><ul><ul><li>THADA (associated with type II diabetes) </li></ul></ul><ul><ul><li>genes implicated in cognitive ability </li></ul></ul><ul><ul><ul><ul><li>AUTS2, DYRK1A, NRG3, CADPS2 </li></ul></ul></ul></ul><ul><ul><li>RUNX2, associated with cleidocranial dysplasia </li></ul></ul><ul><ul><ul><li>might explain skeletal differences in skull and upper body between AMH and Neanderthals </li></ul></ul></ul>
  25. 37. But are Neanderthals more closely related to some AMHs than to others? <ul><li>Compare sites with derived SNPs in Neanderthals/AMH </li></ul><ul><li>Initial comparison to 2 European Americans, 2 East Asians and 4 West Africans shows Neanderthals significantly closer to non-Africans </li></ul><ul><li>Confirmed by comparisons with San, Yoruba, Han, French, Papuan, which also showed direction of flow is from Neanderthal to non-African humans </li></ul><ul><li>Chromosomal segments identified in which Craig Venter is more Neanderthal than African! </li></ul><ul><li>~1-4% of non-African genome is Neanderthal </li></ul>
  26. 38. Neanderthals AMH European Chinese Papuan West African San
  27. 39. Can molecules tell us anything about what Neanderthals were really like? <ul><li>Specific studies on candidate genes and molecules </li></ul>
  28. 46. Neanderthals AMH European Chinese Papuan West African San Denisovans
  29. 49. Overlap of archaic & AMH in Africa?
  30. 51. Conclusions <ul><li>Now have multiple Neanderthal mtDNA sequences </li></ul><ul><ul><li>All outside the range of human variation </li></ul></ul><ul><li>Neanderthal genome sequence supports the idea of small-scale mixing </li></ul><ul><li>Now have evidence that (some) Neanderthals had pale skin, human-like FOXP2, bitter taste heterozygosity, blood group O </li></ul><ul><li>Other archaic admixture from Denisovans and unknown African population </li></ul><ul><li>More gene and genome sequences promised! </li></ul>
  31. 52. The last word? Are we really that surprised....?!
  32. 53. Recommended viewing <ul><li>Search YouTube: </li></ul><ul><ul><li>For a bad (and I mean bad!) 1970s Neanderthal pop song use search terms “Neanderthal” and “Hotlegs” </li></ul></ul><ul><ul><li>For the amusing comparison of Neanderthals and AMHs, use search terms “Eddie Izzard” and “Neanderthal” </li></ul></ul><ul><li>Links to Chris Stringer’s talk and papers and other material available via WebCT </li></ul>
  33. 54. Image sources and rights <ul><li> Some rights reserved by erix! </li></ul><ul><li> Some rights reserved By Jorge Lucero </li></ul><ul><li> CC BY-SA 2.0 Ryan Somma </li></ul><ul><li>Stanislav Kozlovskiy GNU Free Documentation License, V 1.2 </li></ul><ul><li> Luna04 GNU Free Documentation License, Version 1. </li></ul><ul><li> GNU Free Documentation License, Version 1.2 We El </li></ul><ul><li> </li></ul><ul><li> </li></ul><ul><li> </li></ul><ul><li> </li></ul><ul><li> </li></ul><ul><li>Jason Potter CC-BY-SA-2.5 </li></ul><ul><li> CC BY-NC-SA 2.0 Massmatt </li></ul><ul><li> </li></ul><ul><li> </li></ul><ul><li> </li></ul><ul><li>Chris Stringer kindly provided last two slides </li></ul>.