Natural selection for the Duffy-null allele in the recently admixed people of Madagascar

• Published in: Proceedings of the Royal Society. B, Biological sciences Vol. 281; no. 1789; p. 20140930
• Main Authors: Hodgson, Jason A., Pickrell, Joseph K., Pearson, Laurel N., Quillen, Ellen E., Prista, António, Rocha, Jorge, Soodyall, Himla, Shriver, Mark D., Perry, George H.
• Format: Journal Article
• Language: English
• Published: England The Royal Society 22.08.2014
• Subjects: Adaptive Evolution; Africa South of the Sahara; African Continental Ancestry Group - genetics; Asian Continental Ancestry Group - genetics; Computer Simulation; Duffy Blood Group; Duffy Blood-Group System - genetics; Gene Frequency; Genetic Drift; Genetics, Population; Humans; Madagascar; Malagasy Population Genetics; Migration; Models, Genetic; Polymorphism, Single Nucleotide; Receptors, Cell Surface - genetics; Selection, Genetic; Vivax Malaria; Africa South of the Sahara; Madagascar; ISW, Indian Ocean, Madagascar; Asia; Africa; migration; Duffy blood group; Malagasy population genetics; adaptive evolution; vivax malaria
• ISSN: 0962-8452; 1471-2954
• DOI: 10.1098/rspb.2014.0930

While gene flow between distantly related populations is increasingly recognized as a potentially important source of adaptive genetic variation for humans, fully characterized examples are rare. In addition, the role that natural selection for resistance to vivax malaria may have played in the extreme distribution of the protective Duffy-null allele, which is nearly completely fixed in mainland sub-Saharan Africa and absent elsewhere, is controversial. We address both these issues by investigating the evolution of the Duffy-null allele in the Malagasy, a recently admixed population with major ancestry components from both East Asia and mainland sub-Saharan Africa. We used genome-wide genetic data and extensive computer simulations to show that the high frequency of the Duffy-null allele in Madagascar can only be explained in the absence of positive natural selection under extreme demographic scenarios involving high genetic drift. However, the observed genomic single nucleotide polymorphism diversity in the Malagasy is incompatible with such extreme demographic scenarios, indicating that positive selection for the Duffy-null allele best explains the high frequency of the allele in Madagascar. We estimate the selection coefficient to be 0.066. Because vivax malaria is endemic to Madagascar, this result supports the hypothesis that malaria resistance drove fixation of the Duffy-null allele in mainland sub-Saharan Africa.