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  Recent adaptive acquisition by African rainforest hunter-gatherers of the late Pleistocene sickle-cell mutation suggests past differences in malaria exposure

Laval, G., Peyrégne, S., Zidane, N., Harmant, C., Renaud, F., Patin, E., et al. (2019). Recent adaptive acquisition by African rainforest hunter-gatherers of the late Pleistocene sickle-cell mutation suggests past differences in malaria exposure. The American Journal of Human Genetics, 104(3), 553-561. doi:10.1016/j.ajhg.2019.02.007.

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 Urheber:
Laval, Guillaume, Autor
Peyrégne, Stéphane1, 2, Autor                 
Zidane, Nora, Autor
Harmant, Christine, Autor
Renaud, François, Autor
Patin, Etienne, Autor
Prugnolle, Franck, Autor
Quintana-Murci, Lluis, Autor
Affiliations:
1Department of Evolutionary Genetics, Max Planck Institute for Evolutionary Anthropology, Max Planck Society, ou_1497672              
2The Leipzig School of Human Origins (IMPRS), Max Planck Institute for Evolutionary Anthropology, Max Planck Society, Deutscher Platz 6, 04103 Leipzig, DE, ou_1497688              

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Schlagwörter: rainforest hunter-gatherers; farmers, malaria; sickle mutation; balancing selection; approximate Bayesian computation; Africa
 Zusammenfassung: The hemoglobin βS sickle mutation is a textbook case in which natural selection maintains a deleterious mutation at high frequency in the human population. Homozygous individuals for this mutation develop sickle-cell disease, whereas heterozygotes benefit from higher protection against severe malaria. Because the overdominant βS allele should be purged almost immediately from the population in the absence of malaria, the study of the evolutionary history of this iconic mutation can provide important information about the history of human exposure to malaria. Here, we sought to increase our understanding of the origins and time depth of the βS mutation in populations with different lifestyles and ecologies, and we analyzed the diversity of HBB in 479 individuals from 13 populations of African farmers and rainforest hunter-gatherers. Using an approximate Bayesian computation method, we estimated the age of the βS allele while explicitly accounting for population subdivision, past demography, and balancing selection. When the effects of balancing selection are taken into account, our analyses indicate a single emergence of βS in the ancestors of present-day agriculturalist populations ∼22,000 years ago. Furthermore, we show that rainforest hunter-gatherers have more recently acquired the βS mutation from the ancestors of agriculturalists through adaptive gene flow during the last ∼6,000 years. Together, our results provide evidence for a more ancient exposure to malarial pressures among the ancestors of agriculturalists than previously appreciated, and they suggest that rainforest hunter-gatherers have been increasingly exposed to malaria during the last millennia.

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Sprache(n): eng - English
 Datum: 2019-03-07
 Publikationsstatus: Erschienen
 Seiten: -
 Ort, Verlag, Ausgabe: -
 Inhaltsverzeichnis: -
 Art der Begutachtung: Expertenbegutachtung
 Identifikatoren: DOI: 10.1016/j.ajhg.2019.02.007
 Art des Abschluß: -

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Titel: The American Journal of Human Genetics
Genre der Quelle: Zeitschrift
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Ort, Verlag, Ausgabe: Amsterdam : Elsevier
Seiten: - Band / Heft: 104 (3) Artikelnummer: - Start- / Endseite: 553 - 561 Identifikator: ISSN: 0002-9297