University of Khartoum

Effects of Natural Selection and Gene Conversion on the Evolution of Human Glycophorins Coding for MNS Blood Polymorphisms in Malaria-Endemic African Populations

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dc.contributor.author Ibrahim, Muntaser E.
dc.contributor.author Froment, Alain
dc.contributor.author Lema, Godfrey
dc.contributor.editor en_US
dc.contributor.other Molecular Biology en_US
dc.date 2011-06
dc.date.accessioned 2015-11-16T11:30:50Z
dc.date.available 2015-11-16T11:30:50Z
dc.date.issued 2015-11-16
dc.date.submitted 2015
dc.identifier.uri http://khartoumspace.uofk.edu/123456789/17154
dc.description.abstract Malaria has been a very strong selection pressure in recent human evolution, particularly in Africa. Of the one million deaths per year due to malaria, more than 90% are in sub-Saharan Africa, a region with high levels of genetic variation and population substructure. However, there have been few studies of nucleotide variation at genetic loci that are relevant to malaria susceptibility across geographically and genetically diverse ethnic groups in Africa. Invasion of erythrocytes by Plasmodium falciparum parasites is central to the pathology of malaria. Glycophorin A (GYPA) and B (GYPB), which determine MN and Ss blood types, are two major receptors that are expressed on erythrocyte surfaces and interact with parasite ligands.We analyzed nucleotide diversity of the glycophorin gene family in 15 African populations with different levels of malaria exposure. High levels of nucleotide diversity and gene conversion were found at these genes. We observed divergent patterns of genetic variation between these duplicated genes and between different extracellular domains of GYPA. Specifically, we identified fixed adaptive changes at exons 3–4 of GYPA. By contrast, we observed an allele frequency spectrum skewed toward a significant excess of intermediate-frequency alleles at GYPA exon 2 in many populations; the degree of spectrum distortion is correlated with malaria exposure, possibly because of the joint effects of gene conversion and balancing selection.We also identified a haplotype causing three amino acid changes in the extracellular domain of glycophorin B. This haplotype might have evolved adaptively in five populations with high exposure to malaria. en_US
dc.language.iso en en_US
dc.publisher UOFK en_US
dc.subject Natural Selection en_US
dc.subject Gene Conversion en_US
dc.subject Human Glycophorins Coding en_US
dc.subject MNS Blood Polymorphisms en_US
dc.subject Malaria-Endemic en_US
dc.subject African Populations en_US
dc.title Effects of Natural Selection and Gene Conversion on the Evolution of Human Glycophorins Coding for MNS Blood Polymorphisms in Malaria-Endemic African Populations en_US
dc.type Publication en_US
dc.Faculty Endemic Diseases en_US


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