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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
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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
"
12
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)
13
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
14
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?
15
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)
16
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
17
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
18
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
19
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
20
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
21
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
23
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.
24
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.
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