Population genetic analysis of the DARC locus (Duffy) reveals adaptation from standing variation associated with malaria resistance in humans

• DOI: 10.1371/journal.pgen.1006560
• Publication Date: 2017-03-10T18:25:39Z
• Authors: Kimberly F. McManus; Angela M. Taravella; Brenna M. Henn; Carlos D. Bustamante; Martin Sikora; Omar E. Cornejo
• Keywords: Selective sweep; 1000 Genomes Project; Demographic history; Complement receptor 1

The human DARC (Duffy antigen receptor for chemokines) gene encodes a membrane-bound chemokine crucial the infection of red blood cells by Plasmodium vivax, major causative agent malaria. Of three allelic classes segregating in populations, FY*O allele has been shown to protect against P. vivax and is at near fixation sub-Saharan Africa, while FY*B FY*A are common Europe Asia, respectively. Due combination strong geographic differentiation association with malaria resistance, considered canonical example positive selection humans. Despite this, details timing mode remain poorly understood. Here, we use sequencing data from over 1,000 individuals twenty-one as well ancient genomes, perform fine-scale investigation evolutionary history DARC. We estimate time most recent ancestor (TMRCA) haplotype be 42 kya (95% CI: 34-49 kya). infer null mutation swept Africa standing variation very low initial frequency (0.1%) coefficient 0.043 CI:0.011-0.18), which among strongest estimated genome. TMRCA non-Africans 57 48-65 kya) that, prior sweep FY*O, all alleles were highly diverged populations Asia ≠Khomani San hunter-gatherers share same haplotypes. test multiple models admixture that may account this observation reject Asian or European cause.