High Levels of Genetic Diversity within Nilo-Saharan Populations: Implications for Human Adaptation

Abstract

Summary Africa contains more human genetic variation than any other continent, but the majority of the population-scale analyses of the African peoples have focused on just two of the four major linguistic groups, the Niger-Congo and Afro-Asiatic, leaving the Nilo-Saharan and Khoisan populations under-represented. In order to assess genetic variation and signatures of selection within a Nilo-Saharan population and between the Nilo-Saharan and Niger-Congo and Afro-Asiatic, we sequenced 50 genomes from the Nilo-Saharan Lugbara population of North-West Uganda and 250 genomes from 6 previously unsequenced Niger-Congo populations. We compared these data to data from a further 16 Eurasian and African populations including the Gumuz, another putative Nilo-Saharan population from Ethiopia. Of the 21 million variants identified in the Nilo-Saharan population, 3.57 million (17%) were not represented in dbSNP and included predicted non-synonymous mutations with possible phenotypic effects. We found greater genetic differentiation between the Nilo-Saharan Lugbara and Gumuz populations than between any two Afro-Asiatic or Niger-Congo populations. F3 tests showed that Gumuz contributed a genetic component to most Niger-Congo B populations whereas Lugabara did not. We scanned the genomes of the Lugbara for evidence of selective sweeps. We found selective sweeps at four loci ( SLC24A5 , SNX13 , TYRP1 , and UVRAG ) associated with skin pigmentation, three of which already have been reported to be under selection. These selective sweeps point toward adaptations to the intense UV radiation of the Sahel.

High-depth African genomes inform human migration and health

“…These two loci are known to be protective against severe malaria, which is endemic in Uganda. Historically, differences in HbS frequencies between these groups were attributed to the relatively recent spread of malaria to NS populations; however, our results, and other recent findings 41 , suggest that recent migration from northern regions, where malaria is less common (UNS), as opposed to from malaria-endemic western regions (UBS) is another plausible explanation 42 . A similar argument can be made for the APOL1 high-risk G1 and G2 alleles, which have been shown to provide protection against specific Trypanosoma species 12 .…”

Unmapped exome reads implicate a role for Anelloviridae in childhood HIV-1 long-term non-progression

“…Because LTNPs were older than the RPs, and thus, would have had a longer temporal exposure to environmental viruses (see “Results”), we utilised an external dataset of WGS from 33 adults from central Uganda, collected under the TrypanoGEN study 92 , 93 , and similarly sequenced on the Illumina HiSeq 2500 (Illumina, San Diego, CA) as age-related controls. Unmapped reads from this dataset were also run through the VirusFinder v2.0 pipeline with identical parameters to the WES dataset.…”

SNX-PXA-RGS-PXC Subfamily of SNXs in the Regulation of Receptor-Mediated Signaling and Membrane Trafficking

“…There is a dynamic coordinated interaction among the recycling, retrograde, and degradative pathways, which maintains normal cellular functions [ 2 , 3 ]. However, if the SNX-PXA-RGS-PXC subfamily, like all other SNX subfamilies, is dysfunctional and disabled to transport receptor cargoes to their appropriate cellular destinations, there will be the impairment of the above-mentioned pathways, which will negatively affect cellular functions, causing disorders, such as those listed in Table 4 [ 17 , 18 , 19 , 20 , 23 , 27 , 33 , 38 , 89 , 90 , 91 , 92 , 93 , 94 , 95 , 96 , 97 , 98 ].…”