Whole-genome sequencing reveals a complex African population demographic history and signatures of local adaptation

Shaohua Fan; Jeffrey P Spence; Yuanqing Feng; Matthew E B Hansen; Jonathan Terhorst; Marcia H Beltrame; Alessia Ranciaro; Jibril Hirbo; William Beggs; Neil Thomas; Thomas Nyambo; Sununguko Wata Mpoloka; Gaonyadiwe George Mokone; Alfred Njamnshi; Charles Folkunang; Dawit Wolde Meskel; Gurja Belay; Yun S Song; Sarah A Tishkoff

doi:10.1016/j.cell.2023.01.042

Whole-genome sequencing reveals a complex African population demographic history and signatures of local adaptation

Cell. 2023 Mar 2;186(5):923-939.e14. doi: 10.1016/j.cell.2023.01.042.

Authors

Shaohua Fan¹, Jeffrey P Spence², Yuanqing Feng³, Matthew E B Hansen³, Jonathan Terhorst⁴, Marcia H Beltrame³, Alessia Ranciaro³, Jibril Hirbo³, William Beggs³, Neil Thomas⁵, Thomas Nyambo⁶, Sununguko Wata Mpoloka⁷, Gaonyadiwe George Mokone⁸, Alfred Njamnshi⁹, Charles Folkunang¹⁰, Dawit Wolde Meskel¹¹, Gurja Belay¹¹, Yun S Song¹², Sarah A Tishkoff¹³

Affiliations

¹ State Key Laboratory of Genetic Engineering, Human Phenome Institute, Zhangjiang Fudan International Innovation Center, School of Life Science, Fudan University, Shanghai, 200438, China; Department of Genetics, University of Pennsylvania, Philadelphia, PA 19104, USA.
² Department of Genetics, School of Medicine, Stanford University, Stanford, CA 94305, USA.
³ Department of Genetics, University of Pennsylvania, Philadelphia, PA 19104, USA.
⁴ Department of Statistics, University of Michigan, Ann Arbor, MI 48109, USA.
⁵ Computer Science Division, University of California, Berkeley, Berkeley, CA 94720, USA.
⁶ Department of Biochemistry, Kampala International University in Tanzania, P.O. Box 9790, Dar es Salaam, Tanzania.
⁷ Department of Biological Sciences, Faculty of Science, University of Botswana Gaborone, Private Bag UB 0022, Gaborone, Botswana.
⁸ Department of Biomedical Sciences, Faculty of Medicine, University of Botswana Gaborone, Private Bag UB 0022, Gaborone, Botswana.
⁹ Department of Neurology, Central Hospital Yaoundé; Brain Research Africa Initiative (BRAIN), Neuroscience Lab, Faculty of Medicine and Biomedical Sciences, The University of Yaoundé I, P.O. Box 337, Yaoundé, Cameroon.
¹⁰ Department of Pharmacotoxicology and Pharmacokinetics, Faculty of Medicine and Biomedical Sciences, The University of Yaoundé I, P.O. Box 337, Yaoundé, Cameroon.
¹¹ Department of Microbial Cellular and Molecular Biology, Addis Ababa University, P.O. Box 1176, Addis Ababa, Ethiopia.
¹² Computer Science Division, University of California, Berkeley, Berkeley, CA 94720, USA; Department of Statistics, University of California, Berkeley, Berkeley, CA 94720, USA; Chan Zuckerberg Biohub, San Francisco, CA 94158, USA.
¹³ Department of Genetics, University of Pennsylvania, Philadelphia, PA 19104, USA; Department of Biology, University of Pennsylvania, Philadelphia, PA 19104, USA. Electronic address: tishkoff@pennmedicine.upenn.edu.

Abstract

We conduct high coverage (>30×) whole-genome sequencing of 180 individuals from 12 indigenous African populations. We identify millions of unreported variants, many predicted to be functionally important. We observe that the ancestors of southern African San and central African rainforest hunter-gatherers (RHG) diverged from other populations >200 kya and maintained a large effective population size. We observe evidence for ancient population structure in Africa and for multiple introgression events from "ghost" populations with highly diverged genetic lineages. Although currently geographically isolated, we observe evidence for gene flow between eastern and southern Khoesan-speaking hunter-gatherer populations lasting until ∼12 kya. We identify signatures of local adaptation for traits related to skin color, immune response, height, and metabolic processes. We identify a positively selected variant in the lightly pigmented San that influences pigmentation in vitro by regulating the enhancer activity and gene expression of PDPK1.

Keywords: African demographic history; African genomics; Khoesan; archaic introgression; gene regulation; human evolution; local adaptation; natural selection; population structure; skin color.

Publication types

Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural

MeSH terms

3-Phosphoinositide-Dependent Protein Kinases
Acclimatization*
Africa
Humans
Population Density
Skin Pigmentation*
Whole Genome Sequencing

Substances

PDPK1 protein, human
3-Phosphoinositide-Dependent Protein Kinases

Abstract

Publication types

MeSH terms

Substances

Grants and funding