Title: Tracing Pastoralist Migrations to Southern Africa with Lactase Persistence Alleles
Abstract: Although southern African Khoisan populations are often assumed to have remained largely isolated during prehistory, there is growing evidence for a migration of pastoralists from eastern Africa some 2,000 years ago [1Ehret C. Cattle-keeping and milking in eastern and southern African history - linguistic evidence.J. Afr. Hist. 1967; 8: 1-17Crossref Scopus (43) Google Scholar, 2Güldemann T. A linguist’s view: Khoe-Kwadi speakers as the earliest food-producers of southern Africa.South Afr. Humanit. 2008; 20: 93-132Google Scholar, 3Henn B.M. Gignoux C. Lin A.A. Oefner P.J. Shen P. Scozzari R. Cruciani F. Tishkoff S.A. Mountain J.L. Underhill P.A. Y-chromosomal evidence of a pastoralist migration through Tanzania to southern Africa.Proc. Natl. Acad. Sci. USA. 2008; 105: 10693-10698Crossref PubMed Scopus (101) Google Scholar, 4Pickrell J.K. Patterson N. Loh P.R. Lipson M. Berger B. Stoneking M. Pakendorf B. Reich D. Ancient west Eurasian ancestry in southern and eastern Africa.Proc. Natl. Acad. Sci. USA. 2014; 111: 2632-2637https://doi.org/10.1073/pnas.1313787111Crossref PubMed Scopus (170) Google Scholar, 5Pleurdeau D. Imalwa E. Détroit F. Lesur J. Veldman A. Bahain J.J. Marais E. “Of sheep and men”: earliest direct evidence of caprine domestication in southern Africa at Leopard Cave (Erongo, Namibia).PLoS ONE. 2012; 7: e40340Crossref PubMed Scopus (73) Google Scholar], prior to the arrival of Bantu-speaking populations in southern Africa. Eastern Africa harbors distinctive lactase persistence (LP) alleles [6Jensen T.G.K. Liebert A. Lewinsky R. Swallow D.M. Olsen J. Troelsen J.T. The -14010∗C variant associated with lactase persistence is located between an Oct-1 and HNF1α binding site and increases lactase promoter activity.Hum. Genet. 2011; 130: 483-493Crossref PubMed Scopus (36) Google Scholar, 7Jones B.L. Raga T.O. Liebert A. Zmarz P. Bekele E. Danielsen E.T. Olsen A.K. Bradman N. Troelsen J.T. Swallow D.M. Diversity of lactase persistence alleles in Ethiopia: signature of a soft selective sweep.Am. J. Hum. Genet. 2013; 93: 538-544Abstract Full Text Full Text PDF PubMed Scopus (59) Google Scholar, 8Tishkoff S.A. Reed F.A. Ranciaro A. Voight B.F. Babbitt C.C. Silverman J.S. Powell K. Mortensen H.M. Hirbo J.B. Osman M. et al.Convergent adaptation of human lactase persistence in Africa and Europe.Nat. Genet. 2007; 39: 31-40Crossref PubMed Scopus (988) Google Scholar], and therefore LP alleles in southern African populations may be derived from this eastern African pastoralist migration. We sequenced the lactase enhancer region in 457 individuals from 18 Khoisan and seven Bantu-speaking groups from Botswana, Namibia, and Zambia and additionally genotyped four short tandem repeat (STR) loci that flank the lactase enhancer region. We found nine single-nucleotide polymorphisms, of which the most frequent is −14010∗C, which was previously found to be associated with LP in Kenya and Tanzania and to exhibit a strong signal of positive selection [8Tishkoff S.A. Reed F.A. Ranciaro A. Voight B.F. Babbitt C.C. Silverman J.S. Powell K. Mortensen H.M. Hirbo J.B. Osman M. et al.Convergent adaptation of human lactase persistence in Africa and Europe.Nat. Genet. 2007; 39: 31-40Crossref PubMed Scopus (988) Google Scholar]. This allele occurs in significantly higher frequency in pastoralist groups and in Khoe-speaking groups in our study, supporting the hypothesis of a migration of eastern African pastoralists that was primarily associated with Khoe speakers [2Güldemann T. A linguist’s view: Khoe-Kwadi speakers as the earliest food-producers of southern Africa.South Afr. Humanit. 2008; 20: 93-132Google Scholar]. Moreover, we find a signal of ongoing positive selection in all three pastoralist groups in our study, as well as (surprisingly) in two foraging groups.