Whole Genome Sequencing Reveals Ancient African Substructure and Local Adaptation | Duke Kunshan University

Whole Genome Sequencing Reveals Ancient African Substructure and Local Adaptation

E.g., 06/18/2022
E.g., 06/18/2022
Jan 15th 2019
12:00 to 13:00
Academic Building 1079

Summary of talk: 

Africa is the origin of modern humans and is the source of human migrations across the globe within the last 100,000 years. However, Africans are still underrepresented in modern human genomic studies. We conducted high cover- age (>30X) whole genome sequencing of 180 individuals from 12 indigenous African populations from Eastern, Western, and Southern Africa, which cover a wide range of subsistence patterns, languages, and phenotypic variation. We found a total of 33.6 million SNPs of which ~5 million SNPs were not re- ported in the dbSNP database (version 150) and 34% were predicted to be of functional significance, indicating the importance of including ethnically diverse Africans in genomics studies. Phylogenetic reconstruction found that the San populations have lineages that are basal to all modern human lineages. The location of other African populations on the phylogeny largely correlates with their current geographic locations, with the exception of the Pygmies, whose lineages cluster near the San. Admixture analysis identified a shared ancestry among African hunter-gatherer populations from southern, eastern and central Africa, suggesting an ancient connection among these populations. Based on coalescence analysis, we find evidence of population structure in Africa emerging as early as 250 kya, with the earliest divergence between the ancestors of the San and other African populations. We also see evidence for an ancient divergence of all hunter-gatherer populations (San, Pygmy, Hadza, Sandawe) >80 kya. PSMC analysis indicates that ancient effective population sizes of populations begins to differentiate at ~250 kya, close to the time of emergence of modern humans. Despite a small current census size, the ancestors of the San and Pygmy populations maintained the largest (Ne) from ~50–250 kya. We also observe evidence for a recent population bottleneck in the Hadza that resulted in a current size of only ~1,000 individuals. We also identified signatures of positive selection in each population, which may contribute to their local adaptation and phenotypic variation. For example, positively selected SNPs in the Pygmy population are statistically enriched for pathways involving bone growth and cartilage development, which may relate to their short stature. In the San, the SNPs that are under positive selection are significantly enriched in pathways that are associated with skin pigmentation.

Brief Biography:

Dr. Fan graduated from Northwest Agriculture and Forestry University in 2008 with a master degree in Molecular Chemistry and Molecular Biology and then got his Ph.D. degree in Evolutionary Biology from University of Konstanz, Germany 2014. He had his postdoctoral training in the Department of Genetics at University of Pennsylvania, USA from 2015 to 2018. In August 2018, Dr. Fan starts to work as co-PI at the School of Life Sciences and Human Phenome Institute, Fudan University, China. Dr. Fan’s research interests include: demographic history and population structure of modern human; local adaptation of modern human; the impact of genomic structure variation to human phenotypic variation.