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Barbujani leicester

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EMBO Conference presentation: Human evolutionary genetics

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Barbujani leicester

  1. 1. Human evolutionary genetics A few questions for the next few years Guido Barbujani Dipartimento di Scienze della Vita e Biotecnologie Università di Ferrara g.barbujani@unife.it Leicester, April 1st, 2014
  2. 2. ER Mardis (2011) Nature 470: 198-203 doi:10.1038/nature09796 Revolutionary changes in our ability to generate genetic data over the past decade Date Time taken N authors Cost (US dollars) 2003 (HGP) 13 years 2,800 2.7 billion 2007 (Venter) 4 years 31 100 million 2008 (Watson) 4.5 months 27 1.5 million Oct. 2008 342,502 Oct. 2009 little 70,333 Oct. 2010 29,092 Oct. 2012 6,618 Oct. 2013 2.5 days (exome) 5,096 http://www.genome.gov/sequencingcosts/
  3. 3. Questions concerning three things: 1. Hybridisation between human forms vs. the Southern route of modern human expansion from Africa 2. Evolution of cognitive functions vs. relationships between cultural and biological diversity 3. Data on human genome diversity vs. persistence of the racial paradigm
  4. 4. 1. Hybridisation vs. Southern route Han Papuan French Yoruba San
  5. 5. 1. Hybridisation vs. Southern route
  6. 6. Hybridisation events proposed on the basis of HLA data. Is this a parsimonious hypothesis? Abi-Rached et al. (2011) Science 334: 89-94 1. Hybridisation vs. Southern route Population Freq. Papua Wosera 20.5 % Australia Kimberley 8.3 % China Yunnan 9.0 % Israeli Jews 3.0 % Albanians 2.5 % Finnish 1.1 %
  7. 7. A simpler, and currently rather standard, view of likely hybridisation processes. 1. Hybridisation vs. Southern route Stoneking and Krause (2011) Nature Rev Genet 12: 603-614 Wall, J. D. et al. (2013) Genetics 194: 199–209
  8. 8. Henn et al. (2012) Proc Natl Acad Sci USA 109: 17758-17764 1. Hybridisation vs. Southern route Scally and Durbin (2012) Nature Rev Genet 13: 745-753
  9. 9. Nei and Roychoudhury (1993) Mol Biol Evol. 10: 927-943 Separation times from African populations PREDICTION: Under SD we expect equal separation times from Africa for Europe and Asia; under MD we expect significantly different separation times from Africa for Europe and Asia 1. Hybridisation vs. Southern route
  10. 10. FST = Genetic distance LINKAGE DISEQUILIBRIUM T = Separation time Ne = eff. population size But things are not so simple Hayes et al. (2003) Novel multilocus measure of linkage disequilibrium to estimate past effective population size. Genome Res 13: 635-643 McVean (2002) A genealogical interpretation of linkage disequilibrium. Genetics 162: 987-991 1. Hybridisation vs. Southern route
  11. 11. SINGLE DISPERSALMULTIPLE DISPERSAL 1MULTIPLE DISPERSAL 2 1. Hybridisation vs. Southern route
  12. 12. Africa Europa W.Asia C.Asia E.Asia S.Asia S.E.Asia Oceania Population sizes inferred from LD values Holsinger and Weir (2009) Nature Rev Genet. 10: 639-650 1. Hybridisation vs. Southern route McEvoy et al. (2011) Genome Res. 21: 821-829
  13. 13. Significantly older separation between Africa and East Asia / Oceania than between Africa and Europe Lower 5% CL Estimate (years ago) Higher 5% CL Europe 69,768 74,209 77,448 East Asia + Oceania 79,007 82,862 87,925 Oceania 92,609 97,799 104,142 1 generation = 25 years 1. Hybridisation vs. Southern route
  14. 14. 1. Hybridisation vs. Southern route
  15. 15. 1. Hybridisation vs. Southern route Reyes-Centeno et al. Proc Natl Acad Sci USA (2014) in press
  16. 16. If most Papuans’ ancestors arrived via a Southern route, they missed by 1,000 miles the nearest Neandertal with whom they could hybridize Any better hypothesis? 1. Hybridisation vs. Southern route A problem with the hybridization models
  17. 17. 1. Hybridisation vs. Southern route
  18. 18. Another little problem In all well-studied cases of hybridization, females of the invaded population were incorporated in the invading population. However, Neandertal mtDNA has never been observed in any current human population 1. Hybridisation vs. Southern route
  19. 19. Perhaps that’s not a problem? An interbreeding success smaller than 2% for Neanderthal-human hybrids is fully compatible with limited Neanderthal nuclear introgression and with no introgression of mtDNA. But perhaps it is? Observed statistics ABC, Approximate Bayesian Computations Comparison of observed diversity statistics with those generated under alternative models Currat and Excoffier (2011) Proc Natl Acad Sci USA 105: 15129-15134 1. Hybridisation vs. Southern route
  20. 20. Model 4, with no Neandertals contribution to the mitochondrial genealogy, is at least 8 times as likely as any alternative coalescent- based model 1. Hybridisation vs. Southern route Ghirotto et al. (2011) Am J Phys Anthropol 146: 242-252.
  21. 21. Adding gene flow from Neandertals into the modern mtDNA pool decreases the posterior probability with respect to a model with no admixture 1. Hybridisation vs. Southern route Ghirotto et al. (2011) Am J Phys Anthropol 146: 242-252.
  22. 22. What about the effects of population structure? Neandertals Ancestors of Eurasians Ancestors of Africans 1. Hybridisation vs. Southern route
  23. 23. Evolution of brain size 2. Coevolution of cultural and biological diversity
  24. 24. 2. Coevolution of cultural and biological diversity
  25. 25. 3. Coevolution of cultural and biological diversity
  26. 26. H. erectus H. sapiens Neandertals Trees inferred from morphometrics Neandertals H. erectus H. sapiens LEFT SIDE RIGHT SIDE 2. Coevolution of cultural and biological diversity Di Vincenzo, F., P. Piras & G. Manzi (2012) Proceedings of the European Society for the study of Human Evolution 1: 70.
  27. 27. Castillo-Morales A et al. (2014) Proc. R. Soc. B 281: 20132428. Increased brain size in Mammals correlates with over-representation of gene families not obviously associated with cognitive functions 2. Coevolution of cultural and biological diversity
  28. 28. Somel et al. (2013) Nature Rev. Neurosciences 14: 112-127. 2. Coevolution of cultural and biological diversity So, do we have any evidence for nearly simultaneous origin of language and of the FOXP2 regulatory mutation?
  29. 29. Similarity between gene trees and language trees suggests parallel evolutionary changess Cavalli-Sforza et al. (1988) Proc Natl Acad Sci USA 85: 6002-6006 Populations speaking related languages are also genetically closer than expected based on their spatial distance Sokal (1988) Proc Natl Acad Sci USA 85: 1722-1726 2. Coevolution of cultural and biological diversity
  30. 30. Validation: Mantel Correlations among Indo-European speakers Mantel correlation r P Lexical-geographic 0.206 0.077 Syntactic-geographic 0.385 0.008 Lexical-genomic 0.514 0.0001 Syntactic-genomic 0.491 0.0004 Lexical-syntactic 0.822 0.0001 LanGeLin: Inferring linguistic relationships from structural language features, in grammar and synthax 2. Coevolution of cultural and biological diversity
  31. 31. Jaccard distances inferred from syntactic distances Application: A European language tree Basque English Finnish French German Greek Hungarian Irish Italian Polish Portuguese Rumanian Russian Serbo_Croat Spanish Basque 0.0000 English 0.3333 0.0000 Finnish 0.3000 0.3600 0.0000 French 0.3600 0.2000 0.3333 0.0000 German 0.3913 0.0857 0.3333 0.1579 0.0000 Greek 0.6364 0.3529 0.4074 0.2973 0.2632 0.0000 Hungarian 0.4167 0.3103 0.1429 0.3529 0.3548 0.3548 0.0000 Irish 0.5294 0.1429 0.4167 0.2121 0.1250 0.2727 0.4286 0.0000 Italian 0.3600 0.1579 0.3103 0.0476 0.1220 0.2308 0.2941 0.2353 0.0000 Polish 0.4286 0.3077 0.2857 0.2414 0.1613 0.2000 0.3571 0.2308 0.2000 0.0000 Portuguese 0.3077 0.1579 0.3103 0.0476 0.1220 0.2500 0.3143 0.2121 0.0222 0.2000 0.0000 Rumanian 0.4286 0.2353 0.3077 0.1579 0.2432 0.2105 0.3125 0.2903 0.1000 0.2593 0.1000 0.0000 Russian 0.4286 0.3077 0.2857 0.2667 0.1875 0.2000 0.3571 0.2308 0.2258 0.0303 0.2258 0.2593 0.0000 Serbo_Croat 0.4286 0.2800 0.2593 0.2667 0.1613 0.2000 0.3333 0.2308 0.2258 0.0625 0.2258 0.2593 0.0303 0.0000 Spanish 0.3600 0.1892 0.3571 0.0698 0.1500 0.2500 0.3714 0.2000 0.0667 0.2414 0.0222 0.1000 0.2667 0.2667 0.0000 2. Coevolution of cultural and biological diversity
  32. 32. How come that black athletes always win in Olympic running events? Isn’t that the sign of a racial difference? 3. Racial paradigms
  33. 33. We are not identical, and our physical aspect contains information on our likely place of origin 3. Racial paradigms
  34. 34. The study of morphology leads to contrasting racial catalogs Linnaeus (1735) 4 (europeus, luridus, afer, americanus) [+2] Buffon (1749) 6 (european, lapp, tartar, asian, ethiopan, american) Blumenbach (1795) 5 (caucasian, malay, afer, americanus, australianus) Cuvier (1828) 3 (caucasoid, negroid, mongoloid) Huxley (1875) 4 (mongoloid, xanthocroid, australoid, negroid) Deniker (1900) 29 Von Eickstedt (1937) 38 Chicago Nat. Hist. Museum (1933) 107 USA census (2000) 6: White, Black or African-American, American Indian and Alaska Native, Asian, Native Hawaiian and other Pacific Islander, Hispanic or Latino USA census (2010) 15: White, Black or African-American, American Indian and Alaska Native, Asian Indian, Chinese, Filipino, Japanese, Korean, Vietnamese, Other Asian, Native Hawaiian, Guamanian, Samoan, Other Pacific Islander, Hispanic or Latino 3. Racial paradigms
  35. 35. Frank Livingstone: An alternative scientific paradigm, continuous variation 3. Racial paradigms
  36. 36. Theodosius Dobzhansky: Genetic diversity and human equality “Equality—as in equality in law and equality of opportunity—pertains to the rights and the sacredness of life of every human being and not to the individual’s bodily or mental features. There are valid races in humans, but biology is only beginning to properly define them”. 3. Racial paradigms
  37. 37. Pre- and post-genomic estimates of genetic variances Lewontin (1972) 85% 8% 6% Barbujani et al. (1997) 85% 5% 10% Jorde et al. (2000) 85% 2% 13% Romualdi et al. (2002) 83% 8% 9% Rosenberg et al. (2002) 93% 3% 4% Excoffier & Hamilton (2003) 88% 3% 9% Ramachandran et al. (2005) 90% 5% 5% Bastos-Rodriguez et al. (2006) 86% 2% 12% Li et al. (2008) 89% 2% 9% Barreiro et al. (2008) 89% 11% Auton et al. (2009) 95% 5% Xing et al. (2009) 88% 12% MEDIAN within populations between populations between races or continents 85% 5% 10% 3. Racial paradigms
  38. 38. At the genomic level, two people from the same country can be more different than people from different continents Within-population diversity is very large 3. Racial paradigms Ahn et al. (2008) Genome Res 19: 1622-1629
  39. 39. “To attain truly personalized medicine, the scientific community must leave behind simplistic race-based approaches, and look instead for the genetic and environmental factors contributing to individual drug reactions” 3. Racial paradigms Ng et al. (2008) Clin Pharmacol Ther. 84: 306-309
  40. 40. Hence, the human genome produces a consistent molecular architecture in the prefrontal cortex, despite millions of genetic differences across individuals and races. It's significantly possible that the Clovis population is of mixed race -- and Kennewick Man and Spirit Cave Man actually came with the Old Cordilleran 149352 papers as of March 13, 2014 3. Racial paradigms
  41. 41. Many thanks to: Krishna Veeramah Tomàs Marques-Bonet Richard Nichols Silvietta Ghirotto Fabio Di Vincenzo
  42. 42. Denisova Possible area of admixture with Neandertal Possible area of admixture with Denisovans (H. heidelbergensis?) Possible area of admixture with H. rhodesiensis Veeramah and Hammer (2014) Nature Reviews Genetics 15: 149–162 1. Hybridisation vs. Southern route
  43. 43. Initial dataset 871 populations 2471 individuals > 1 million SNPs Final dataset 63 populations 1672 individuals 95,401 SNPs 1. Hybridisation vs. Southern route
  44. 44. Harmonic means over arbitrary recombination classes; errors estimated comparing Ne values inferred for the different chromosomes Estimated population sizes inferred from LD values 1. Hybridisation vs. Southern route
  45. 45. Each of us shares 99.9% of her genome with everybody else Two cells of the same person 0/1000 Two identical twins 0/1000 Two of us 1/1000 One of us and a chimp 10-30/1000 One of us and an artichoke 700/1000 3. Racial paradigms
  46. 46. In each individual, chromosomes are mosaics of DNA traits of different origins From the 23andme.com and Gedmatch.co m sites

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