Estimating Ancestry and Genetic Diversity in Admixed Populations.

107 Pages·2016·1.34 MB·English

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Anthony Koehl
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Anthony Joseph Koehl
Candidate
Anthropology
Department
Thisdissertationisapproved,anditisacceptableinqualityandformforpublication:
Approved by the Dissertation Committee:
JeffreyLongPhD,Chair
KeithHunleyPhD,Member
OsbjornPearsonPhD,Member
LindsaySmithPhD,Member
MarkShriverPhD,Member
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Estimating Ancestry and Genetic Diversity
in Admixed Populations
BY
Anthony Joseph Koehl
B.S. Anthropology, Northern Kentucky University, 2003
M.S. Human Biology, University of Indianapolis, 2009
M.A. Anthropology, University of New Mexico, 2013
Dissertation
SubmittedinPartialFulfillmentofthe
RequirementsoftheDegreeof
DoctorofPhilosophy
Anthropology
TheUniversityofNewMexico
Albuquerque,NewMexico
January,2016
ii
ACKNOWLEDGMENTS
I wish to wholeheartedly acknowledge Dr. Jeffrey Long, my doctoral advisor and dis-
sertation chair, who worked tirelessly to advance me through this stage of my career. Dr.
Long’s commitment in the classroom provided me with the knowledge to undertake this
research. His door was always open, which allowed me to advance my research and my
understanding of genetics and for that I am eternally grateful. He is the greatest teacher
I have had and the best student I have ever seen. Dr. Long has been committed to me
throughthisprocessasmymentor,andIhopethatasIadvancemycareerhewillmaintain
thatcommitmentasacolleagueandasafriend.
In addition, I wish to thank my committee members, Dr. Keith Hunley, Dr. Ozzie
Pearson,Dr. MarkShriver,andDr. LindsaySmith,fortheirinsightinimprovingthiswork
and for advancing me as a professional in the field of anthropology. I hope to have the
opportunitytocollaboratewithalloftheminthefuture.
Finally, to my friends and family, without you I could not have succeeded in this en-
deavor. Iamforeverthankfultoyouforyoursupport,andcamaraderie.
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EstimatingAncestryandGeneticDiversityinAdmixedPopulations
by
AnthonyJosephKoehl
B.S.Anthropology,NorthernKentuckyUniversity,2003
M.S.HumanBiology,UniversityofIndianapolis,2009
M.A.Anthropology,UniversityofNewMexico,2013
Ph.D.Anthropology,UniversityofNewMexico
ABSTRACT
Admixture is a form of gene flow that occurs when long separated populations come
into contact and exchange mates. Admixture has been a primary mechanism in the for-
mation of many modern human populations. The genetic characteristics of an admixed
population are intermediate to, yet distinct from, those of its ancestors. In this disserta-
tion, I investigate biological and statistical factors that enter into the analysis of admixed
populations using genetic marker data. In chapters one and two, I use genotype data from
published sources that contain 618 microsatellite loci. In chapter three, I simulate geno-
typesof500microsatelliteloci.
In chapter two, I present an analysis of genetic diversity within and among 17 pop-
ulations in the Americas that were formed by admixture among continental Indigenous
Americans, Africans and Europeans. This is the first application of a new method to parti-
tion the genetic distance between pairs of populations into components related to ancestry
and genetic drift. I show that the genetic relationships among the continental sources and
genetic drift occurring after population formation strongly influence the genetic structure
ofthesepopulations.
In chapter three, I investigate a new strategy to find modern populations to serve as
models for ancestors in admixture events that occurred in the past. This is a long-standing
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challenge to admixture studies. This chapter focuses on the Cape Coloured people of
South Africa, a population that formed by mixture of indigenous Africans, Europeans,
andAsians. IproposeaseriesofmodelsfortheirancestryandusetheAkaikeInformation
Criterion to choose the best model. This method from information theory identifies a sim-
plemodelthatproposesonlyAfricanandAsianancestors. Iinterpretthisresultintermsof
boththeprincipleofparsimonyandtheevolutionaryrecentcommonancestorofthehuman
species.
Inchapterfour,Iusecomputersimulationstoassessbiasinancestryfractionsestimated
byusingmaximumlikelihood. Thesenovelsimulationsweredesignedtoproducedatasets
thatmimicactualpatternsofvariationinhumanpopulations. Ihavefoundsamplingstrate-
giesthatproducereasonablyunbiasedresults,despitethepotentialformaximumlikelihood
toproducebiasedestimates.
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Contents
1 Introduction 1
2 The Contributions of Admixture and Genetic Drift to Diversity Among Post-
ContactPopulationsintheAmericas 6
2.1 Overview . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6
2.2 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7
2.3 PopulationGeneticModel . . . . . . . . . . . . . . . . . . . . . . . . . . 8
2.4 MaterialsandMethods . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11
2.5 Results . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17
2.6 Discussion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 29
3 Identifying the Number of Source Populations and Their Identities in Genetic
AncestryAnalyses 33
3.1 Overview . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 33
3.2 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 34
3.3 FoundingoftheCapeColouredPeople . . . . . . . . . . . . . . . . . . . . 36
3.4 MaterialsandMethods . . . . . . . . . . . . . . . . . . . . . . . . . . . . 39
3.5 Results . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 44
3.6 Discussion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 50
4 Using Contemporary Populations as Pseudo-Ancestors to Estimate Ancestry
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Fractions 53
4.1 Overview . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 53
4.2 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 54
4.3 MaterialsandMethods . . . . . . . . . . . . . . . . . . . . . . . . . . . . 56
4.4 Results . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 63
4.5 Discussion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 75
5 Conclusion 80
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List of Figures
2.1 Schematicshowingtheindependentcontributionsofadmixtureandgenetic
drifttogeneticdistance. . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9
2.2 Inferredaveragecontinentalancestryof49populations. . . . . . . . . . . . 20
2.3 Principal coordinates one and two of Nei’s minimum genetic distances
amongthe49populationsinouranalysis. . . . . . . . . . . . . . . . . . . 21
2.4 (Top)Positionsofthe17post-contactpopulationsalongtheprincipalEigen
vector of the ancestry component of the genetic distance matrix. (Bottom)
The positions of the 17 post-contact populations along the ten principal
Eigenvectorsofthedriftcomponentofthegeneticdistancematrix. . . . . 27
2.5 Threesetsofpairwisecomparisonswhichdisplaytheiroverallgeneticdis-
tanceandthepercentofthatdistanceduetodrift. . . . . . . . . . . . . . . 29
3.1 TimelineofthemajorhistoricaleventsintheCapeColony. . . . . . . . . . 36
3.2 Twenty-six models, which serve as hypotheses in testing ancestry among
theCapeColouredpopulationofSouthAfrica. . . . . . . . . . . . . . . . 44
3.3 Scatter plots and their R2 values for three of the 26 potential models of
ancestryfortheCapeColouredofSouthAfrica. . . . . . . . . . . . . . . . 47
3.4 The distribution of ancestry fraction estimates among the source regions,
acrossallmodels. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 49
4.1 Apopulationtreethatservesasareferenceforoursimulations. . . . . . . . 57
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4.2 Modelone(left)simulationtoestimateancestryfromthedirectsourcede-
scendants. Model two (right) estimates ancestry fractions from closely re-
latedpseudo-ancestralsources . . . . . . . . . . . . . . . . . . . . . . . . 59
4.3 Modelthree(left)estimatesancestryfromthemostdistantlyrelatedpseudo-
ancestor in each region. Model four (right) estimates ancestry from multi-
plepseudo-ancestorsineachregion. . . . . . . . . . . . . . . . . . . . . . 60
4.4 Model five (left) estimates ancestry in a simulated Latin American pop-
ulation from pseudo-ancestors who are descended from the true ancestral
populations. Model six (right) estimates the ancestry of a simulated Latin
American population from pseudo-ancestors that are closely related to the
trueancestors. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 61
4.5 Model seven (left) estimates the ancestry of a simulated Latin American
population from a distantly related pseudo-ancestor from each continental
region. Model eight (right) estimates the ancestry of a simulated Latin
Americanpopulationfrommultiplepseudo-ancestorspercontinentalregion. 62
4.6 Results from model one, which estimates ancestry in a simulated African-
American population from the pseudo-ancestors that are the descendants
ofthetheancestralsources. . . . . . . . . . . . . . . . . . . . . . . . . . . 64
4.7 Results from model two, which estimates ancestry in a simulate African-
American population from ancestral proxies that are closely related con-
temporarypopulationstotheactualancestralsources. . . . . . . . . . . . . 65
4.8 Resultsfrommodelthree,whichestimatesancestryinasimulatedAfrican-
American population from distantly related pseudo-ancestors to the actual
ancestralsourcesintheircontinentalregions. . . . . . . . . . . . . . . . . 66
4.9 Results from model four, which estimates ancestry in a simulated African-
American population using multiple related pseudeo-ancestors from their
continentalregions. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 68
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