barbujani leicester

Human evolutionary genetics

A few questions for the next few years

Guido BarbujaniDipartimento di Scienze della Vita e BiotecnologieUniversità di [email protected] Leicester, April 1st, 2014

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/

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

1. Hybridisation vs. Southern route

Han

Papuan

French

Yoruba

San

Hybridisation events proposed on the basis of HLA data. Is this a parsimonious hypothesis?

Abi-Rached et al. (2011) Science 334: 89-94


Population Freq.

Papua Wosera 20.5 %

Australia Kimberley 8.3 %

China Yunnan 9.0 %

Israeli Jews 3.0 %

Albanians 2.5 %

Finnish 1.1 %

A simpler, and currently rather standard, view of likely hybridisation processes.


Stoneking and Krause (2011) Nature Rev Genet 12: 603-614

Wall, J. D. et al. (2013) Genetics 194: 199–209

Henn et al. (2012) Proc Natl Acad Sci USA 109: 17758-17764


Scally and Durbin (2012) Nature Rev Genet 13: 745-753

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


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: 635-643McVean (2002) A genealogical interpretation of linkage disequilibrium. Genetics 162: 987-991


SINGLE DISPERSALMULTIPLE DISPERSAL 1MULTIPLE DISPERSAL 2


AfricaEuropaW.AsiaC.AsiaE.AsiaS.AsiaS.E.AsiaOceania

Population sizes inferred from LD values

Holsinger and Weir (2009) Nature Rev Genet. 10: 639-650


McEvoy et al. (2011) Genome Res. 21: 821-829

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



Reyes-Centeno et al. Proc Natl Acad Sci USA (2014) in press

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?


A problem with the hybridization models

Another little problemIn 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


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


Model 4, with no Neandertals contribution to the mitochondrial genealogy, is at least 8 times as likely as any alternative coalescent-

based model


Ghirotto et al. (2011) Am J Phys Anthropol 146: 242-252.

Adding gene flow from Neandertals into the modern mtDNA pool decreases the posterior probability with respect to a model with no

admixture


Ghirotto et al. (2011) Am J Phys Anthropol 146: 242-252.

What about the effects of population structure?

NeandertalsAncestors of EurasiansAncestors of Africans


Evolution of brain size

2. Coevolution of cultural and biological diversity

H. erectus

H. sapiens

Neandertals

Trees inferred from morphometrics

Neandertals

H. erectus

H. sapiens

LEFT SIDE RIGHT SIDE


Di Vincenzo, F., P. Piras & G. Manzi (2012) Proceedings of the European Society for the study of Human Evolution 1: 70.

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


Somel et al. (2013) Nature Rev. Neurosciences 14: 112-127.


So, do we have any evidence for nearly simultaneous origin of language and of the FOXP2 regulatory mutation?

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


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


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 SpanishBasque 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


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

3. Racial paradigms

We are not identical, and our physical aspect contains information on our likely place of origin

3. Racial paradigms

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) 29Von Eickstedt (1937) 38Chicago Nat. Hist. Museum (1933) 107USA 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

Frank Livingstone: An alternative scientific paradigm, continuous variation

3. Racial paradigms

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

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

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

“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

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

Many thanks to:

Krishna Veeramah

Tomàs Marques-Bonet

Richard Nichols

Silvietta Ghirotto Fabio Di Vincenzo

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


Initial dataset871 populations 2471 individuals> 1 million SNPs

Final dataset63 populations 1672 individuals95,401 SNPs


Harmonic means over arbitrary recombination classes; errors estimated comparing Ne values inferred for the different chromosomes

Estimated population sizes inferred from LD values


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

In each individual, chromosomes are mosaics of DNA traits of different origins

From the 23andme.com and Gedmatch.com sites

barbujani leicester

Education

southern route population

southern route stoneking

southern route scally

southern route mcevoy

hybridisation events

southern route reyescenteno

asia e

asia s