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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Date
2011-06-10
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The American Journal of Human Genetics
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 geograph-
ically 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 spec-
trum 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.
Description
Keywords
Malaria, Natural selection, Genes
Citation
Ko, W.Y., Kaercher, K.A., Giombini, E., Marcatili, P., Froment, A., Ibrahim, M., Lema, G., Nyambo, T.B., Omar, S.A., Wambebe, C. and Ranciaro, A., 2011. Effects of natural selection and gene conversion on the evolution of human glycophorins coding for MNS blood polymorphisms in malaria-endemic African populations. The American Journal of Human Genetics, 88(6), pp.741-754.