A comprehensive whole genome sequence scan for positive selection in southern Africa

PROJECT SUMMARY An African origin for modern humans and the vast genetic diversity in the region is irrefutable. Within Africa, southern Africa is home to the some of the oldest and most diverse extant human populations world-wide. These populations, the KhoeSan, reside predominantly in the north-western parts of South Africa and throughout

Namibia and Botswana. In previous work (PMID 27474727), I and two of my mentors showed that fine-scale genetic population structure between these KhoeSan populations reflects ecogeographical boundaries. In addition to this unique KhoeSan ancestry, populations in southern Africa have been shaped by numerous

migrations from within Africa (e.g. Bantu-speaking peoples) and outside Africa (notably European and Asian populations). Thus, the patterns of diversity observed in this area is unique with no comparable regions elsewhere in the world. These southern African populations went on to further adapt to their new environment

which was plagued by disease, resource limitations and harsh climates. The role of positive selection in this adaption, remains unknown. Using one of the largest whole genome sequencing dataset collections encompassing numerous southern African populations, we aim to: 1) scan these datasets for signals of positive selection and 2) evaluate

the functional, biological and potentially translational implications of these signals. This project will be the largest and most comprehensive single study of natural selection on the African continent. The methods developed in this study will inform future scans for natural selection in heterogenous, admixed African populations.

Furthermore, the findings will provide insights into how adaptation to the environment has shaped human genomes and in turn, various phenotypes in this unique part of Africa - these results could be informative to all populations with African ancestry.