Genetic variation in Khoisan-speaking populations from southern Africa

PhD, Faculty of Health Sciences, University of the WitwatersrandThe San and Khoe people currently represent remnant groups of a much larger and widely distributed population of hunter gatherers and cattle herders, respectively, who had exclusive occupation of southern Africa before the arrival of Bantu-speaking groups in the past 1,200 years and sea-borne immigrants within the last 350 years. This project made use of mitochondrial DNA (mtDNA), Y-chromosome DNA and autosomal DNA markers to examine the population structure of various San and Khoe groups and to reconstruct their prehistory. The groups included in the study consists of six different Khoe-San groups (‡Khomani, Nama, Khwe, !Xun, /Gui + //Gana + Kgalagari and Ju\’hoansi), four different Coloured groups and five other population groups that were included in the comparative analysis. For the mtDNA study a minisequencing technique was successfully developed which allowed the assignment of mtDNA lineages into the 10 global mtDNA macro-haplogroups. Haplogroups were further resolved using control region sequence data obtained from both hypervariable regions (HVR I and HVR II). Using this approach 538 individuals (both males and females) were screened and their mtDNA types were resolved into 18 haplogroups encompassing 245 unique haplotypes. In addition, 353 males were examined for Ychromosome DNA variation using 46 bi-allelic Y-chromosome markers and 12 Y-STR markers. The Y-chromosomes in the sample were assigned into 29 haplogroups (using biallelic variation) following the nomenclature initially recommended by the Y-chromosome Consortium and resolved into 268 unique haplotypes (Y-STR variation). To assess the level of autosomal variation, 220 genome wide autosomal SNPs were typed in 352 individuals. These SNPs were combined in different datasets and analysed using two different approaches allowing for genotype and haplotype analyses. Data from these three marker systems were analysed using different analytical methods (distance based phylogenetic analysis, network analysis, dating of lineages, principal components analysis, phylogeographic analysis, AMOVA analysis, population structure analysis, and population genetic summary statistics) to asses the ancestral associations and the genetic affinities of the various San, Khoe and Coloured populations. The most striking observation from this study was the high frequencies of the oldest mtDNA haplogroups (L0d and L0k) and Y-chromosome haplogroups (haplogroups A and B) found in Khoe-San and Coloured groups. The sub-haplogroups were, however, differentially distributed in the different Khoe-San and Coloured groups which suggested different demographic histories. The current distribution of Khoe-San groups comprises a wide geographic region extending from southern Angola in the north to the Cape Province (South Africa) in the south. Linguistically Khoe-San groups are also divided into northern Khoisan-speaking groups (Ju division) and southern Khoisan-speaking groups (Tuu division) with an additional linguistic group (Khoe) associated with some Khoe-speaking San groups in Botswana and the Khoe herders of South Africa and Namibia (such as the Nama). For all three genetic marker systems, northern groups (Ju speaking - !Xun, Ju\’hoansi and Khoe-speaking San - /Gui + //Gana) grouped into one cluster and southern groups (historically Tuu speaking - ‡Khomani and Coloured groups) grouped into a second cluster with the Khoe group (Nama) clustering with the southern Khoe-San and Coloured groups. The Khwe genetic profile was very different from the other Khoe-San groups. Although high proportions of Bantu-speaking admixture were identified in the Khwe group, they also contained a unique distribution of other mtDNA and Y-chromosome lineages. A previously published theory suggested that, based on the presence of a specific E-M35 Ychromosome haplotype, the Khwe might be descendants of an east African pastoralist group that introduced the pastoralist culture to a region located in the present day northern Botswana. This pattern also mirrors what archaeologists have found with respect to the introduction of pastoralism to southern Africa. The theory was further supported and elaborated on in the present thesis. Considering the frequency and distribution of E-M35, the highest frequency (46%) was found in the Khwe with a present-day distribution in northern Botswana and southern Angola while a decrease in frequency is observed towards the south with low frequencies (<10%) in the Karoo Coloured groups. Conversely, none of the mtDNA (female) L0k and L0d lineages observed in the Khwe group were observed in the southern Khoe-San and Coloured groups. From these observations a theory was proposed that after introduction into the region of northern Botswana, the southwards spread of pastoralism was not a clear-cut demic or cultural diffusion. Rather some male individuals integrated with the southern tribes and took with them the pastoralist practice and likely also their Khoe-language. Altogether this thesis presented new insights into the multifaceted demographic history that shaped the existing genetic landscape of the Khoe-San and Coloured populations of southern Africa

Along the Indian Ocean coast : genomic variation in Mozambique provides new insights into the Bantu expansion

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Selenium metabolism to the trimethylselenonium ion (TMSe) varies markedly because of polymorphisms in the indolethylamine N-methyltransferase gene.

Selenium is an essential element, but its metabolism in humans is not well characterized. A few small studies indicate that the trimethylselenonium ion (TMSe) is a common selenium metabolite in humans

Multiple migrations to the Philippines during the last 50,000 years

Island Southeast Asia has recently produced several surprises regarding human history, but the region's complex demography remains poorly understood. Here, we report similar to 2.3 million genotypes from 1,028 individuals representing 115 indigenous Philippine populations and genome-sequence data from two similar to 8,000-y-old individuals from Liangdao in the Taiwan Strait. We show that the Philippine islands were populated by at least five waves of human migration: initially by Northern and Southern Negritos (distantly related to Australian and Papuan groups), followed by Manobo, Sama, Papuan, and Cordilleran-related populations. The ancestors of Cordillerans diverged from indigenous peoples of Taiwan at least similar to 8,000 y ago, prior to the arrival of paddy field rice agriculture in the Philippines similar to 2,500 y ago, where some of their descendants remain to be the least admixed East Asian groups carrying an ancestry shared by all Austronesian-speaking populations. These observations contradict an exclusive "out-of-Taiwan" model of farming-language-people dispersal within the last four millennia for the Philippines and Island Southeast Asia. Sama-related ethnic groups of southwestern Philippines additionally experienced some minimal South Asian gene flow starting similar to 1,000 y ago. Lastly, only a few lowlanders, accounting for &lt;1% of all individuals, presented a low level of West Eurasian admixture, indicating a limited genetic legacy of Spanish colonization in the Philippines. Altogether, our findings reveal a multilayered history of the Philippines, which served as a crucial gateway for the movement of people that ultimately changed the genetic landscape of the Asia-Pacific region

Philippine Ayta possess the highest level of Denisovan ancestry in the world

Multiple lines of evidence show that modern humans interbred with archaic Denisovans. Here, we report an account of shared demographic history between Australasians and Denisovans distinctively in Island Southeast Asia. Our analyses are based on-2.3 million genotypes from 118 ethnic groups of the Philippines, including 25 diverse self-identified Negrito populations, along with high-coverage genomes of Australopapuans and Ayta Magbukon Negritos. We show that Ayta Magbukon possess the highest level of Denisovan ancestry in the world--30%-40% greater than that of Australians and Papuans-consistent with an independent admixture event into Negritos from Denisovans. Together with the recently described Homo luzonensis, we suggest that there were multiple archaic species that inhabited the Philippines prior to the arrival of modern humans and that these archaic groups may have been genetically related. Altogether, our findings unveil a complex intertwined history of modern and archaic humans in the Asia-Pacific region, where distinct Islander Denisovan populations differentially admixed with incoming Australasians across multiple locations and at various points in time