BackgroundGenomic analysis of high-altitude populations residing in the Andes and Tibet has revealed several candidate loci for involvement in high-altitude adaptation, a subset of which have also been shown to be associated with hemoglobin levels, including EPAS1, EGLN1, and PPARA, which play a role in the HIF-1 pathway. Here, we have extended this work to high- and low-altitude populations living in Ethiopia, for which we have measured hemoglobin levels. We genotyped the Illumina 1M SNP array and employed several genome-wide scans for selection and targeted association with hemoglobin levels to identify genes that play a role in adaptation to high altitude.ResultsWe have identified a set of candidate genes for positive selection in our high-altitude population sample, demonstrated significantly different hemoglobin levels between high- and low-altitude Ethiopians and have identified a subset of candidate genes for selection, several of which also show suggestive associations with hemoglobin levels.ConclusionsWe highlight several candidate genes for involvement in high-altitude adaptation in Ethiopia, including CBARA1, VAV3, ARNT2 and THRB. Although most of these genes have not been identified in previous studies of high-altitude Tibetan or Andean population samples, two of these genes (THRB and ARNT2) play a role in the HIF-1 pathway, a pathway implicated in previous work reported in Tibetan and Andean studies. These combined results suggest that adaptation to high altitude arose independently due to convergent evolution in high-altitude Amhara populations in Ethiopia.
African Pygmy groups show a distinctive pattern of phenotypic variation, including short stature, which is thought to reflect past adaptation to a tropical environment. Here, we analyze Illumina 1M SNP array data in three Western Pygmy populations from Cameroon and three neighboring Bantu-speaking agricultural populations with whom they have admixed. We infer genome-wide ancestry, scan for signals of positive selection, and perform targeted genetic association with measured height variation. We identify multiple regions throughout the genome that may have played a role in adaptive evolution, many of which contain loci with roles in growth hormone, insulin, and insulin-like growth factor signaling pathways, as well as immunity and neuroendocrine signaling involved in reproduction and metabolism. The most striking results are found on chromosome 3, which harbors a cluster of selection and association signals between approximately 45 and 60 Mb. This region also includes the positional candidate genes DOCK3, which is known to be associated with height variation in Europeans, and CISH, a negative regulator of cytokine signaling known to inhibit growth hormone-stimulated STAT5 signaling. Finally, pathway analysis for genes near the strongest signals of association with height indicates enrichment for loci involved in insulin and insulin-like growth factor signaling.
Anatomically modern humans arose in Africa ∼300,000 years ago, but the demographic and adaptive histories of African populations are not well-characterized. Here, we have generated a genome-wide dataset from 840 Africans, residing in western, eastern, southern, and northern Africa, belonging to 50 ethnicities, and speaking languages belonging to four language families. In addition to agriculturalists and pastoralists, our study includes 16 populations that practice, or until recently have practiced, a hunting-gathering (HG) lifestyle. We observe that genetic structure in Africa is broadly correlated not only with geography, but to a lesser extent, with linguistic affiliation and subsistence strategy. Four East African HG (EHG) populations that are geographically distant from each other show evidence of common ancestry: the Hadza and Sandawe in Tanzania, who speak languages with clicks classified as Khoisan; the Dahalo in Kenya, whose language has remnant clicks; and the Sabue in Ethiopia, who speak an unclassified language. Additionally, we observed common ancestry between central African rainforest HGs and southern African San, the latter of whom speak languages with clicks classified as Khoisan. With the exception of the EHG, central African rainforest HGs, and San, other HG groups in Africa appear genetically similar to neighboring agriculturalist or pastoralist populations. We additionally demonstrate that infectious disease, immune response, and diet have played important roles in the adaptive landscape of African history. However, while the broad biological processes involved in recent human adaptation in Africa are often consistent across populations, the specific loci affected by selective pressures more often vary across populations.
The continent of Africa is the source of all anatomically modern humans that dispersed across the planet during the past 100,000 years. As such, African populations are characterized by high genetic diversity and low levels of linkage disequilibrium (LD) among loci, as compared to populations from other continents. African populations also possess a number of genetic adaptations that have evolved in response to the diverse climates, diets, geographic environments, and infectious agents that characterize the African continent. Recently, Tishkoff et al. (2009) performed a genomewide analysis of substructure based on DNA from 2432 Africans from 121 geographically diverse populations. The authors analyzed patterns of variation at1327 nuclear microsatellite and insertion/deletion markers and identified 14 ancestral population clusters that correlate well with self described ethnicity and shared cultural or linguistic properties. The results suggest that African populations may have maintained a large and subdivided population structure throughout much of their evolutionary history. In this chapter, we synthesize recent work documenting evidence of African population structure and discuss the implications for inferences about evolutionary history in both African populations and anatomically modern humans as a whole.Africa is a continent of considerable genetic, linguistic, cultural, and phenotypic diversity. It contains more than 2000 distinct ethnolinguistic groups, speaking languages that constitute nearly a third of the world's languages (http://www.ethnologue.com/). The populations within Africa practice a wide range of subsistence patterns, including various modes of agriculture, pastoralism, and hunting and gathering. Africans also live in climates that range from the world's largest desert (the Sahara) and second largest tropical rainforest (the Congo Basin) to savanna, swamps, and mountain highlands. This dramatic range in culture, geography, and diet has given rise to a complex history across the African continent, characterized by high levels of both genetic and phenotypic variation.Africa is also the source of all modern humans, making its populations the oldest and most genetically diverse among the world's human populations. According to the Recent African Origin (RAO) model, anatomically modern humans originated in Africa and then migrated to all other regions of the globe within the past ∼100,000 years (Tishkoff and Verrelli 2003). The transition to modern humans within Africa was not sudden. Rather, the paleobiological record indicates an irregular mosaic of modern, archaic, and regional traits occurring over a sub stantial period of time and across a broad geographic range (McBrearty and Brooks 2000). The earliest known suite of morphological traits associated with modern humans appears in fossil remains from Ethiopia that are dated to ∼150-190 thousand years ago (kya) (White et al. 2003; Correspondence to: S.A. Tishkoff, tishkoff@mail.med.upenn.edu. Patterns of genetic variation in modern ...
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