Abstracts (first author)


Identifying recent Darwinian selection acting on different human APOL1 variants among diverse African populations in trypanosomiasis endemic areas

Author(s): Ko W, Rajan P, Gomez F, Schelinfeldt L, Froment A, Lema G, Nyambo TB, Omar SA, Wambebe C, Ranciaro A, Hirbo JB, Thompson S, Tishkoff SA


Disease susceptibility may arise as a consequence of adaptation to infectious disease. Recent findings have suggested that higher rates of chronic kidney disease (CKD) in individuals with recent African ancestry may be attributed to two APOL1 risk alleles (G1 and G2) at the SRA-interacting domain. These two alleles appear to have risen adaptively, possibly due to their protective effects against African trypanosomiasis (African sleeping sickness). In order to explore the distribution of potential functional variation at APOL1, we studied nucleotide variation in 187 individuals across ten geographically and genetically diverse African ethnic groups with differing levels of exposure to two subspecies of Trypanosoma brucei that cause African sleeping sickness. We observed unusually high levels of nonsynonymous polymorphism at the functional domains that are required to lyse parasites. Whereas allele frequencies of G2 are similar across all populations (3-8%), the G1 allele is only common in the Yoruba (39%). We further identified a previously unreported haplotype (termed G3) that contains a nonsynonymous mutation at the membrane-addressing domain of APOL1 and is present in all populations except for the Yoruba. Analyses of long-range patterns of LD indicate evidence for recent selection acting on the G3 haplotype in Fulani (cattle-herding population) from Cameroon that are endemic to Gambian trypanosomiasis, suggesting its possible protective effects against trypanosome infection. Our results indicate that the G1 and G2 variants are geographically restricted and that there are more candidate variants at other functional domains contributing to trypanosomiasis resistance and risk for CKD in African populations.



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XIV Congress of the European Society for Evolutionary Biology

Organization Team
Department of Animal Biology (DBA)
Faculty of Sciences of the University of Lisbon
P-1749-016 Lisbon


Computational Biology & Population Genomics Group