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.FacultyEndemic Diseasesen_US
dc.contributor.authorIbrahim, Muntaser E.
dc.contributor.authorFroment, Alain
dc.contributor.authorLema, Godfrey
dc.contributor.editoren_US
dc.contributor.otherMolecular Biologyen_US
dc.date2011-06
dc.date.accessioned2015-11-16T11:30:50Z
dc.date.available2015-11-16T11:30:50Z
dc.date.issued2015-11-16
dc.date.submitted2015
dc.description.abstractMalaria 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.identifier.urihttp://khartoumspace.uofk.edu/123456789/17154
dc.language.isoenen_US
dc.publisherUOFKen_US
dc.subjectNatural Selectionen_US
dc.subjectGene Conversionen_US
dc.subjectHuman Glycophorins Codingen_US
dc.subjectMNS Blood Polymorphismsen_US
dc.subjectMalaria-Endemicen_US
dc.subjectAfrican Populationsen_US
dc.titleEffects of Natural Selection and Gene Conversion on the Evolution of Human Glycophorins Coding for MNS Blood Polymorphisms in Malaria-Endemic African Populationsen_US
dc.typePublicationen_US

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