Inferring adaptive gene-flow in recent African history

Abstract

Gene-flow from an ancestrally differentiated group has been shown to be a powerful source of selectively advantageous variants. To understand whether recent gene-flow may have contributed to adaptation among humans in sub-Saharan Africa, we applied a novel method to identify deviations in ancestry inferred from genome-wide data in 48 populations. Among the signals of ancestry deviation that we find in the Fula, an historically pastoralist ethnic group from the Gambia, are the region that encodes the lactose persistence phenotype, LCT/MCM6, which has the highest proportion of Eurasian ancestry in the genome. The region with the lowest proportion of non-African ancestry is across DARC, which encodes the Duffy null phenotype and is protective for Plasmodium vivax malaria. In the Jola from the Gambia and a Khoesan speaking group from Namibia we find multiple regions with inferred ancestry deviation including the Major Histocompatibility Complex. Our analysis shows the potential for adaptive gene-flow in recent human history.

Human Immunology through the Lens of Evolutionary Genetics

“…Two studies revealed that gene flow and admixture within Africa have been accompanied by the exchange of adaptive variants (Busby et al, 2017;Patin et al, 2017). For example, during their dispersal through the rainforest, western Bantuspeaking groups encountered local populations of rainforest hunter-gatherers, with whom they admixed 800 ya and from whom they acquired beneficial alleles in the HLA gene region (Patin et al, 2017) (Figure 3).…”

“…Other studies have provided additional support for the role of HLA as a key substrate for adaptive admixture (Busby et al, 2017). Some HLA haplotypes have been targeted by selection since admixture, as recently as the last few hundred years, as attested by the excess of African ancestry at the HLA locus in some populations from Mexico, Puerto Rico, Colombia and other admixed Hispanic/Latino groups (Rishishwar et al, 2015;Tang et al, 2007;Zhou et al, 2016).…”

“…The case of the Fulani from The Gambia, a population resulting from an admixture event 1,800 ya involving individuals of Eurasian and West African origin, is also worth discussing. Since the admixture event, the Fulani have retained high levels of African ancestry for the ACKR1 (also known as DARC) gene, the null allele of which confers resistance to Plasmodium vivax malaria, and high levels of Eurasian ancestry at the LCT locus, which contains a lactase persistence allele facilitating the digestion of milk in adults (Busby et al, 2017). The highly adaptive nature of the Duffy null allele and its rapid spread across populations via admixture is supported by other studies reporting high African ancestry in admixed populations from Pakistan and Madagascar, where vivax malaria is endemic (Hodgson et al, 2014;Laso-Jadart et al, 2017;Pierron et al, 2018).…”

Something old, something borrowed: Admixture and adaptation in human evolution

“…The increasing availability of ancient and present-day human genomes from Africa will also make it easier to study admixture patterns between modern African populations [71] , or between present-day and archaic human groups in Africa [72][73][74] (Figure 1). As the bulk of human evolution happened in this continent, it will not be surprising to find cases of introgression -and adaptive introgression -between different African human groups, once ancient DNA from Africa becomes more readily available.…”

“…For example, there is some evidence to suggest that the lactase persistence allele located in a regulatory region of the LCT gene -one of the best-known examples of positive selection in humans [68,69] -was perhaps introduced into Western Eurasia via eastward migrations by steppe hereder populations [65,70] . However, the evidence for this hypothesis is still scant, and more ancient sequences will be needed to determine with certainty exactly how this occurred, if it occurred at all [68] .The increasing availability of ancient and present-day human genomes from Africa will also make it easier to study admixture patterns between modern African populations [71] , or between present-day and archaic human groups in Africa [72][73][74] (Figure 1). As the bulk of human evolution happened in this continent, it will not be surprising to find cases of introgression -and adaptive introgression -between different African human groups, once ancient DNA from Africa becomes more readily available.…”