EMBO Conference presentation: Human evolutionary genetics

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. 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. 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. 1. Hybridisation vs. Southern route
Han
Papuan
French
Yoruba
San

5. 1. Hybridisation vs. Southern route

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. 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. 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. 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. 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. SINGLE DISPERSALMULTIPLE DISPERSAL 1MULTIPLE DISPERSAL 2
1. Hybridisation vs. Southern route

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. 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. 1. Hybridisation vs. Southern route

15. 1. Hybridisation vs. Southern route
Reyes-Centeno et al. Proc Natl
Acad Sci USA (2014) in press

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. 1. Hybridisation vs. Southern route

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. 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. 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. 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. What about the effects of population structure?
Neandertals
Ancestors of Eurasians
Ancestors of Africans
1. Hybridisation vs. Southern route

23. Evolution of brain size
2. Coevolution of cultural and biological diversity

24. 2. Coevolution of cultural and biological diversity

25. 3. Coevolution of cultural and biological diversity

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. 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. 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. 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. 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. 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. How come that black athletes always win in Olympic
running events? Isn’t that the sign of a racial difference?
3. Racial paradigms

33. We are not identical, and our physical aspect contains
information on our likely place of origin
3. Racial paradigms

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. Frank Livingstone: An
alternative scientific
paradigm, continuous
variation
3. Racial paradigms

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. 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. 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. “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. 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. Many thanks to:
Krishna Veeramah
Tomàs Marques-Bonet
Richard Nichols
Silvietta Ghirotto Fabio Di Vincenzo

43. 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

44. Initial dataset
871 populations
2471 individuals
> 1 million SNPs
Final dataset
63 populations
1672 individuals
95,401 SNPs
1. Hybridisation vs. Southern route

45. 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

46. 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

47. In each individual, chromosomes are mosaics of DNA
traits of different origins
From the
23andme.com
and
Gedmatch.co
m sites