Article dans une revue
American Journal of Human Genetics
Année : 2019
Recent Adaptive Acquisition by African Rainforest Hunter-Gatherers of the Late Pleistocene Sickle-Cell Mutation Suggests Past Differences in Malaria Exposure
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.
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.
Titre
en
Recent Adaptive Acquisition by African Rainforest Hunter-Gatherers of the Late Pleistocene Sickle-Cell Mutation Suggests Past Differences in Malaria Exposure
1
Génétique Evolutive Humaine - Human Evolutionary Genetics
( 534817 )
- Département Génomes et Génétique - 25-28 rue du Docteur Roux, F-75724 Paris Cedex 15
- France
Institut Pasteur [Paris] ( 300027 )
;
Centre National de la Recherche Scientifique UMR2000 ( 441569 )
2
C3BI -
Centre de Bioinformatique, Biostatistique et Biologie Intégrative
( 463018 )
- 25-28 rue du docteur Roux, 75724 Paris cedex 15
- France
Institut Pasteur [Paris] ( 300027 )
;
Centre National de la Recherche Scientifique USR3756 ( 441569 )
3
Max Planck Institute for Evolutionary Anthropology [Leipzig]
( 308156 )
- Deutscher Pl. 6, 04103 Leipzig
- Allemagne
Max-Planck-Gesellschaft ( 5247 )
4
MIVEGEC -
Maladies infectieuses et vecteurs : écologie, génétique, évolution et contrôle
( 166573 )
- 911 Avenue Agropolis BP 64501 34394 Montpellier cedex 5
- France
Université de Montpellier UMR5290 ( 410122 )
;
Centre National de la Recherche Scientifique UMR5290 ( 441569 )
;
Institut de Recherche pour le Développement 224 ( 451860 )
Page/Identifiant
553-561
Numéro
3
Volume
104
Date de publication électronique
2019-02-28
Date de publication
2019
Audience
Internationale
Comité de lecture
Oui
Vulgarisation
Non
Nom de la revue
AJHG - Am J Hum Genet -
American Journal of Human Genetics
(ISSN : 0002-9297, ISSN électronique : 1537-6605)
Publié par Elsevier (Cell Press)
Revue non référencée dans Sherpa-Romeo
This work was supported by the Institut Pasteur, the Centre National de la Recherche Scientifique (CNRS), and the Agence Nationale de la Recherche (ANR) grants “IEIHSEER” ANR-14-CE14-0008-02, “TBPATHGEN” ANR-14-CE14-0007-02, and “AGRHUM” ANR-14-CE02-0003-01. The laboratory of L.Q.-M. has received funding from the French government’s Investissement d’Avenir program through the Laboratoire d’Excellence “Integrative Biology of Emerging Infectious Diseases” (grant no. ANR-10- LABX-62-IBEID).
Domaine(s)
Sciences du Vivant [q-bio]/Génétique/Génétique des populations [q-bio.PE]
Sciences du Vivant [q-bio]/Génétique/Génétique humaine
Sciences du Vivant [q-bio]/Biodiversité/Evolution [q-bio.PE]
Sciences de l'Homme et Société/Anthropologie biologique
Guillaume Laval, Stéphane Peyrégne, Nora Zidane, Christine Harmant, François Renaud, et al.. Recent Adaptive Acquisition by African Rainforest Hunter-Gatherers of the Late Pleistocene Sickle-Cell Mutation Suggests Past Differences in Malaria Exposure. American Journal of Human Genetics, 2019, 104 (3), pp.553-561. ⟨10.1016/j.ajhg.2019.02.007⟩. ⟨hal-02352993⟩