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.
Highlights
Scans for signatures of recent positive selection in human populations have identified hundreds of candidate loci, suggesting that positive natural selection has been an important force shaping genetic diversity within and between human groups (e.g. [1,2])
The Duffy blood group locus, for which phenotypic consequences are known for a genetic variant [5] that is strongly differentiated between sub-Saharan African and non-African human populations [6], and for which a credible selection pressure hypothesis exists [7], presents an excellent opportunity to examine the role of natural selection in the Malagasy, a recently admixed population with major ancestry components from mainland sub-Saharan Africa and East Asia
A third polymorphism, FY*O or the Duffy-null allele, is a Duffy antigen receptor for chemokines (DARC) promoter region single nucleotide polymorphism (SNP) that effects the loss of Duffy antigen protein expression on red blood cells [5]
Summary
Scans for signatures of recent positive selection in human populations have identified hundreds of candidate loci, suggesting that positive natural selection has been an important force shaping genetic diversity within and between human groups (e.g. [1,2]). The Duffy blood group locus (the DARC gene), for which phenotypic consequences are known for a genetic variant [5] that is strongly differentiated between sub-Saharan African and non-African human populations [6], and for which a credible selection pressure hypothesis exists [7], presents an excellent opportunity to examine the role of natural selection in the Malagasy, a recently admixed population with major ancestry components from mainland sub-Saharan Africa and East Asia. We test the null hypothesis that genetic drift alone can explain the difference between the observed and expected frequencies of the Duffy-null allele in Madagascar, against an alternative hypothesis of a recent history of positive selection, using a series of computer simulations and genomic SNP data from Malagasy and comparative population samples
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callMore From: Proceedings of the Royal Society B: Biological Sciences
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
