1

The Evolution of HumansOver The Last 2 Million

Years:

Genes, Fossils, &Archaeology

All fossilsfound inAfrica

Found in Africa, Europe and

Asia

2

What Do GenesTell Us?

Genes As “Fossils”

Haplotype Tree

3

A Haplotype Tree Should NeverBe Equated To A Tree of

Human Populations. It Is OnlyThe Tree of The Genetic

Variation For That DNA Region.There Is Information AboutPopulation History in the

Haplotype Tree, But It Must BeExtracted Carefully.

InferringEvolutionaryHistory From

HaplotypeTrees

Nested CladePhylogeographic

Analysis

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Nested Clade Analysis

• Converts Haplotype Trees Into A NestedStatistical Design

• Other Data (Phenotypic or Geographical)Are Then Overlaid Upon The NestedDesign

• Statistical Tests Are Performed To DetectSignificant Associations Between theData and The Haplotype Tree

Only When Statistical SignificanceIs Achieved Is The BiologicalSignificance Interpreted With

Explicit, a priori Criteria•For Example, Under Isolation By Distance, ItTakes Many Generations For A New Haplotype ToSpread Across Many Populations.•Therefore, Expect Older Haplotypes To Be MoreWidespread Than Younger Haplotypes•Younger Haplotypes Tend To Have GeographicalRanges Nested Within the Ranges of TheirAncestral Haplotypes

5

Significant Gene Flow WithIsolation By Distance in aHuman mtDNA Haplotype

Tree

26

112

13

15

2325

4041

42

45

46

505662

7266

73

7549

1-11-2

1-3

1-41-5

1-7

1-17

1-18

2-12-2 2-4 2-3

{

{

{2-52-6

2-7

3-1 3-2

{

EuropeAfrica

Asia

Excoffier L, and Langaney A (1989) Origin and differentiation ofhuman mitochondrial DNA. Am. J. Hum. Genet. 44:73-85.

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Nested CladePhylogeographic Analysis

• Recurrent Gene Flow, Range Expansion andFragmentation Could All Have Occurred atDifferent Times and/or Places.

• NCPA Therefore Looks For Multiple Patterns, NotJust One

• The Relative Temporal Ordering of Events in aNested Series of Clades Is Also Inferred by NCPA

• The Validity of NCPA Inferences Was TestedWith Actual Data Sets With 150 a prioriExpectations And Did Very Well. The MostCommon Error Was Failure to Detect An Event,And False Inferences Were Rare

Inference Errors in Nested Clade Analysis

All of these errors can be minimized by studying multiple lociand requiring each inference (type, place and time) to becorroborated by two or more loci.

• Requires Adequate Sampling To ObtainStatistical Significance. NCPA can also haveambiguous biological inference due toinadequate geographical sampling.

• Inference Requires That An Appropriate MutationOccurred At the Right Time and Right Place:Therefore, Some Events and Processes AreMissed With A Particular DNA Region.

• Selection and Evolutionary Stochasticity CanDistort The Distribution of Haplotypes in Spaceand Time, Therefore Leading to False Inferences.

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Performed Nested Clade Analyses on25 DNA Regions

• Mitochondrial DNA (Ingman et al. Nature 408, 708 - 713, 2000: Sykeset al. American Journal of Human Genetics 57, 1463-1475, 1995; Torroni et al. American Journalof Human Genetics 53, 563-590, 1993, American Journal of Human Genetics 53, 591-608, 1993).

• Y-DNA (Hammer et al. Molecular Biology and Evolution 15, 427-441, 1998)• 11 X-Linked Regions (Balciuniene et al. 2001; Garrigan et al. 2005;

Hammer et al. 2004; Harris. & Hey, 1999, 2001; Kaessmann et al. 1999; Nachman et al. 2004;Saunders et al. 2002; Verrelli et al. 2002; Yu et al. 2002)

• 12 Autosomal Genes (Bamshad et al. 2002, Harding et al. 1997; Holloxet al. 2001; Jin et al. 1999; Koda et al. 2001; Rana et al. 1999; Rogers et al. 2000; Toomajian andKreitman 2002; Wooding et al. 2002; Zhang & Rosenberg 2000).

Expected Coalescence Times

4NefAutosomal DNA

3NefX-Linked DNA

NefY-ChromosomalDNA

NefMitochondrial DNA

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Mean and Variance ofCoalescence Time

For an Autosomal Locus:Mean = 4Nef

Variance = 4.64(Nef)2

Estimated Times To Common Ancestor(Method of Takahata et al. 2001)

Dh Nuc.Diff.Within Humans

Dhc Nuc.Diff.Between Humans

& Chimps

6 Million Years Ago

TMRCA = 12Dh/Dhc

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Estimated Times To The CommonAncestor (Method of Takahata et al. 2001)

* Older than the Human/Chimp Split That is Set to 6.0 MYA.

*

Cross-Validation of Inferences

• Concordance of Inference Type andGeographical Location AreStraightforward

• E.g., the 25 DNA regions collectively yield15 inferences of Range Expansion(concordance of inference type) going outof Africa to Eurasia (concordance ofgeographical location)

• Cross-Validation Also RequiresConcordance in Time

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Estimate Time of Event orProcess By Age of Youngest

Haplotype or Clade thatContributes to Inference In a

Statistically SignificantFashion

Estimate the distribution of the age ofthe haplotype or clade as a GammaDistribution with mean T (the age

estimate of Takahata et al. 2001) andVariance T2/(1+k)

where k is the average pairwisedivergence among present day

haplotypes derived from the haplotypebeing aged, measured as the number

of nucleotide differences

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Gamma Distributions For Out-of-Africa Inferences

!

G = "2 (1+ ki) 1"ti

ˆ T + ln ti " ln

ˆ T # $ %

& ' (

i=1

j

)

A Likelihood Ratio Test of TheHypothesis That The Estimated Timesof An Event From j Loci Are The Same

!

ˆ T =

ti(1+ ki )

i=1

j

"

(1+ ki )

i=1

j

"

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The log likelihood ratio test rejects the null hypothesis that all 15 eventsare temporally concordant with a probability value of 3.89 × 10-15.

P = 0.95

P = 0.51

P = 0.62

Three Out-of-Africa Events, All DefinedBy Three or More Loci With A High

Degree of Temporal HomogeneityBut With Highly Significant

Heterogeneity BetweenThe Three Events

There Were At Least Three Out-of-Africa Expansion Events Over

the Last 2 Million Years

0.9937-3.09691.9007

0.3917-0.97450.6508

0.0965-0.16930.1304

95% Confidence RangeTime of Expansion

(Millions of Years Ago)

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Gamma Distributions ForAfrican/Eurasian Gene Flow Inferences

With Isolation By DistanceExtensive overlap implies cross-validationwith the exception of MX1, the only locuswith most of its probability mass in the Pliocene.

The lack of clusters implies therewas no prolonged breaks in geneflow throughout the Pleistocene

Temporal Congruence in Means Is NotNecessary for Recurrent Processes

Such as Gene Flow, But Can CombineSeveral Loci Together To DetermineThe Probability of Gene Flow By A

Given T in the Past.

!

Pr(gene flow by T ) =1"tikie"ti (1+ ki ) / Ti

Ti

1 + ki

#

$ %

&

' (

1 + ki

)(1 + ki )0

T

*i=1

j

+ dti

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African/Eurasian Gene Flow Has ExistedFor At Least 1.46 MY with 95%

Confidence (excluding MX1)

Can All of TheseInferences Be IntegratedInto A Single Overview ofRecent Human Evolution?

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Homo erectus ExpandsOut of Africa at 1.9 MYA,as Shown By Fossil Data

And Molecular Data

A Multi-LocusReconstruction

of HumanEvolution Over

the Past 2Million Years

Allfossils

found inAfrica

Found in Africa, Europe and

Asia

Homo erectus ExpandsOut of Africa at 1.9 MYA,as Shown By Fossil Data

And Molecular Data

By Using ModernHumans, Chimpsand Gorillas as

Models, AQuantitative

Genetic OverlayUpon FacialMorphologyRevealed A

Relaxation ofSelection At This

Time, Indicating ASignificantIncrease in

Reliance UponCulture & Tools(Ackermann &

Cheverud, PNAS101: 17946, 2004)

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Homo erectus ExpandsOut of Africa at 1.9 MYA,as Shown By Fossil Data

And Molecular Data

Agusti J, Kiladze G,Mouskhelishvili A, Nioradze M,de Leon MSP, Tappen M, andZollikofer CPE (2005)Anthropology: The earliesttoothless hominin skull. Nature434:717.

Homo erectus ExpandsOut of Africa at 1.9 MYA,as Shown By Fossil Data

And Molecular Data

As A Consequence,The Human FaceProbably Evolved

As A MostlyNeutral Trait

Associated WithSelection for

Increased CranialCapacity And CanBe Predicted WellUsing The GrowthModels Of Modern

Chimps and Gorillas

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Homo erectus ExpandsOut of Africa at 1.9 MYA,as Shown By Fossil Data

And Molecular Data

Was this initial colonization of Eurasia by Homo erectus permanent or didthey go extinct (Dennel, J. Human Evol. 45: 421-440, 2003)?

With NCPA, The Only Events Detectable Are Those Involving PopulationsThat Left Genetic Descendants In the Current Populations Sampled.

The 1.9 MYA Expansion Event WasDetected By 3 loci, and There is aContinuous Record of Gene FlowInvolving Eurasian Populations

Throughout the Pleistocene.

Therefore, the initialcolonization of Eurasia by

Homo erectus was a permanentone for the human lineage

A Multi-LocusReconstruction

of HumanEvolution Over

the Past 2Million Years

1.9 MYA

Gene Flow Between Africanand Eurasian Populations

With Isolation By Distance by1.46 MYA With 95%

Confidence

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1.9 MYA

Second Expansion Out ofAfrica 0.65 MYA, as Shown By

Genetic Data, the AcheuleanExpansion and an Increase in

Cranial Capacity

1.9 MYA

A Major Archaeological Question IsWhether The Acheulean ExpansionWas The Spread of a Culture or The

Spread Of Populations With TheCulture?

The Detection of A Major PopulationRange Expansion Out of Africa At

This Time Indicates It Was TheSpread of Acheulean Populations

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1.9 MYA

Did These Acheulean PopulationsReplace (Drive to Extinction) TheNon-Acheulean Populations That

They Encountered in Eurasia?Since NCPA Can Only Detect Events

In Populations That Left Descendants,If Replacement Occurred, There

Should be No Eurasian InferencesOlder Than the Acheulean Expansion.

Any Event Older ThanThis Exceeds The 1%

Older Tail of The PooledAcheulean Gamma

Distribution.This Includes the 1.9 MYAHomo erectus Expansion

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Any Event Older ThanThis Exceeds The 1%

Older Tail of The PooledAcheulean Gamma

Distribution.This Includes Two Gene

Flow Events (MX1Excluded)

The log-likelihood Ratio Test Rejects The Hypothesis ofTotal Acheulean Replacement With p =0.0346

A Multi-LocusReconstruction

of HumanEvolution Over

the Past 2Million Years

1.9 MYA

0.65 MYA

Gene Flow Between Africanand Eurasian PopulationsWith Isolation By DistanceWith 99.99% Confidence

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Third Out of Africa Expansion0.096 to 0.169 MYA; Spread of

“Modern” Traits Out ofAfrica, But Many “Modern”Traits Are Still Polymorphic

and There is TemporalContinuity Of Other Traits

1.9 MYA

0.65 MYA

A Multi-LocusReconstruction

of HumanEvolution Over

the Past 2Million Years

The 1%Tail Of The Third Out-of-Africa ExpansionEvent is At 0.1774 MYA. The Log-Likehood Ratio Test

Of The Hypothesis That There Were No EarlierEurasian Events Yields a p-value < 10-17

Therefore, This ExpansionWas Also CharacterizedBy Interbreeding, Not

Replacement.Interbreeding AlsoExplains The Fossil

Pattern of A MixtureOf Spreading Traits

And RegionallyContinuous Traits

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0.3

0.2

1000 2000 3000 4000 5000

Geographic Distance in Miles

0.0

0.1

fst(x)

A Multi-LocusReconstruction

of HumanEvolution Over

the Past 2Million Years

Gene Flow With Isolation ByDistance Continues, But Now

With Some Long DistanceDispersal. Expansions OccurOut of Asia Back to Europe &Africa (Male Mediated) andInto Northern Eurasia, thePacific, and the Americas

0.13 MYA

1.9 MYA

0.65 MYA

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All of The InferencesValidated By Two Or MoreGenes Define a Coherent

Overview of RecentHuman Evolution That Is

Consistent With TheFossil & Archaeological

Record.

Two DominantThemes

• Out-of-Africa Expansions.Populations of African origin dominaterecent human evolution, although not

exclusively.

• Genetic Interchange.Recurrent gene flow with isolation by

distance dominates human history,with occasional range expansions

resulting in interbreeding, notreplacement.

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Implications

• All living humans are from a singleevolutionary lineage that has evolved asa cohesive unit for at least the past1,460,000 years because of gene flow.

• There are no biological races in humans.• Current human populations show genetic

differences, but these are smallcompared to other species of large-bodied mammals and primarily reflectgeographical distance.