title: Natural selection for the Duffy-null allele in the recently admixed people of Madagascar.
abstract: 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.
authors.affiliation: Department of Anthropology, The Pennsylvania State University, University Park, PA 16802, USA Department of Life Sciences, Imperial College London, Silwood Park Campus, Ascot, Berkshire SL5 7PY, UK j.hodgson@imperial.ac.uk.
authors.forename: Jason A
authors.initials: JA
authors.lastname: Hodgson
authors.affiliation: New York Genome Center, New York, NY 10013, USA Department of Biological Sciences, Columbia University, New York, NY 10027, USA.
authors.forename: Joseph K
authors.initials: JK
authors.lastname: Pickrell
authors.affiliation: Department of Anthropology, The Pennsylvania State University, University Park, PA 16802, USA.
authors.forename: Laurel N
authors.initials: LN
authors.lastname: Pearson
authors.affiliation: Department of Anthropology, The Pennsylvania State University, University Park, PA 16802, USA Department of Genetics, Texas Biomedical Research Institute, San Antonio, TX 78245, USA.
authors.forename: Ellen E
authors.initials: EE
authors.lastname: Quillen
authors.affiliation: Faculdade de Educação Física e Desporto, Universidade Pedagógica, Maputo, Moçambique.
authors.forename: António
authors.initials: A
authors.lastname: Prista
authors.affiliation: Centro de Investigação em Biodiversidade e Recursos Genéticos da Universidade do Porto (CIBIO), Vairão, Portugal Departamento de Biologia, Faculdade de Ciências da Universidade do Porto, Porto, Portugal.
authors.forename: Jorge
authors.initials: J
authors.lastname: Rocha
authors.affiliation: Human Genomic Diversity and Disease Research Unit, Division of Human Genetics, School of Pathology, Faculty of Health Sciences, University of Witwatersrand and the National Health Laboratory Service, Johannesburg 2000, South Africa.
authors.forename: Himla
authors.initials: H
authors.lastname: Soodyall
authors.affiliation: Department of Anthropology, The Pennsylvania State University, University Park, PA 16802, USA.
authors.forename: Mark D
authors.initials: MD
authors.lastname: Shriver
authors.affiliation: Department of Anthropology, The Pennsylvania State University, University Park, PA 16802, USA Department of Biology, The Pennsylvania State University, University Park, PA 16802, USA ghp3@psu.edu.
authors.forename: George H
authors.initials: GH
authors.lastname: Perry
mesh_terms: D017954:Africa South of the Sahara; D044466:Asian People / Q000235:genetics; D044383:Black People / Q000235:genetics; D003198:Computer Simulation; D004375:Duffy Blood-Group System / Q000235:genetics*; D005787:Gene Frequency; D040961:Genetic Drift; D005828:Genetics, Population; D006801:Humans; D008270:Madagascar; D008957:Models, Genetic; D020641:Polymorphism, Single Nucleotide; D011956:Receptors, Cell Surface / Q000235:genetics*; D012641:Selection, Genetic
chemical_list: C473745:ACKR1 protein, human; D004375:Duffy Blood-Group System; D011956:Receptors, Cell Surface
keywords: Duffy blood group; Malagasy population genetics; adaptive evolution; migration; vivax malaria