title: Out of Africa: modern human origins special feature: explaining worldwide patterns of human genetic variation using a coalescent-based serial founder model of migration outward from Africa.
abstract: Studies of worldwide human variation have discovered three trends in summary statistics as a function of increasing geographic distance from East Africa: a decrease in heterozygosity, an increase in linkage disequilibrium (LD), and a decrease in the slope of the ancestral allele frequency spectrum. Forward simulations of unlinked loci have shown that the decline in heterozygosity can be described by a serial founder model, in which populations migrate outward from Africa through a process where each of a series of populations is formed from a subset of the previous population in the outward expansion. Here, we extend this approach by developing a retrospective coalescent-based serial founder model that incorporates linked loci. Our model both recovers the observed decline in heterozygosity with increasing distance from Africa and produces the patterns observed in LD and the ancestral allele frequency spectrum. Surprisingly, although migration between neighboring populations and limited admixture between modern and archaic humans can be accommodated in the model while continuing to explain the three trends, a competing model in which a wave of outward modern human migration expands into a series of preexisting archaic populations produces nearly opposite patterns to those observed in the data. We conclude by developing a simpler model to illustrate that the feature that permits the serial founder model but not the archaic persistence model to explain the three trends observed with increasing distance from Africa is its incorporation of a cumulative effect of genetic drift as humans colonized the world.
authors.affiliation: Center for Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI 48109-2218, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: DeGiorgio
authors.forename: Mattias
authors.initials: M
authors.lastname: Jakobsson
authors.forename: Noah A
authors.initials: NA
authors.lastname: Rosenberg
mesh_terms: D000349:Africa; D000818:Animals; D000885:Anthropology, Physical / Q000379:methods; D005075:Biological Evolution; D019143:Evolution, Molecular; D005580:Fossils; D018703:Founder Effect; D014644:Genetic Variation; D005828:Genetics, Population; D006579:Heterozygote; D015186:Hominidae / Q000033:anatomy & histology / Q000145:classification / Q000235:genetics*; D006801:Humans; D015810:Linkage Disequilibrium; D008957:Models, Genetic; D011157:Population Dynamics
references.citation: Science. 2009 May 22;324(5930):1035-44
references.pmid: 19407144
references.citation: Biol Rev Camb Philos Soc. 2009 May;84(2):245-57
references.pmid: 19391204
references.citation: Am J Phys Anthropol. 2009 May;139(1):35-46
references.pmid: 19226641
references.citation: Curr Biol. 2005 Mar 8;15(5):R159-60
references.pmid: 15753023
references.citation: Nat Rev Genet. 2006 Sep;7(9):669-80
references.pmid: 16921345
references.citation: Philos Trans R Soc Lond B Biol Sci. 2002 Apr 29;357(1420):563-79
references.pmid: 12028792
references.citation: PLoS Biol. 2004 Mar;2(3):E57
references.pmid: 15024415
references.citation: Science. 2006 Nov 17;314(5802):1113-8
references.pmid: 17110569
references.citation: PLoS Genet. 2006 Jul;2(7):e105
references.pmid: 16895447
references.citation: Heredity (Edinb). 2008 Jun;100(6):555-63
references.pmid: 18322457
references.citation: Proc Biol Sci. 2009 Jan 22;276(1655):291-300
references.pmid: 18796400
references.citation: Mol Biol Evol. 2001 Feb;18(2):172-83
references.pmid: 11158376
references.citation: Nature. 2006 Nov 16;444(7117):330-6
references.pmid: 17108958
references.citation: Am J Phys Anthropol. 2000 May;112(1):129-36
references.pmid: 10766948
references.citation: Science. 2008 Feb 22;319(5866):1100-4
references.pmid: 18292342
references.citation: PLoS Genet. 2008 May 23;4(5):e1000078
references.pmid: 18497854
references.citation: Nat Rev Genet. 2008 Jun;9(6):477-85
references.pmid: 18427557
references.citation: Am J Hum Genet. 2006 Aug;79(2):230-7
references.pmid: 16826514
references.citation: Genetics. 2002 Jun;161(2):873-88
references.pmid: 12072481
references.citation: Genetics. 2005 Feb;169(2):1061-70
references.pmid: 15489538
references.citation: Genome Res. 2005 Nov;15(11):1576-83
references.pmid: 16251467
references.citation: Mol Biol Evol. 2009 Mar;26(3):501-12
references.pmid: 18988687
references.citation: Bioinformatics. 2002 Feb;18(2):337-8
references.pmid: 11847089
references.citation: Proc Natl Acad Sci U S A. 2007 Nov 6;104(45):17614-9
references.pmid: 17978179
references.citation: Genetics. 1974 Feb;76(2):379-90
references.pmid: 4822472
references.citation: Proc Natl Acad Sci U S A. 2005 Nov 1;102(44):15942-7
references.pmid: 16243969
references.citation: Nat Genet. 2003 Mar;33 Suppl:266-75
references.pmid: 12610536
references.citation: Nature. 2008 Feb 21;451(7181):998-1003
references.pmid: 18288195