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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
Effects of natural selection and gene conversion on the evolution of human glycophorins coding for MNS blood polymorphisms in malaria-endemic African populations
American Journal of Human Genetics, Volume 88, No. 6, Year 2011
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Description
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. © 2011 The American Society of Human Genetics.
Available Materials
https://efashare.b-cdn.net/share/pmc/articles/PMC3113242/bin/mmc1.pdf
Authors & Co-Authors
Ko, Wenya
United States, Philadelphia
University of Pennsylvania
Kaercher, Kristin A.
United States, Philadelphia
University of Pennsylvania
Giombini, E.
Italy, Rome
Sapienza Università Di Roma
Marcatili, Paolo
Italy, Rome
Sapienza Università Di Roma
Froment, Alain
France, Paris
Museé de L'homme
Ibrahim, Muntaser Eltayeb
Sudan, Khartoum
Institute of Endemic Diseases Sudan
Lema, Godfrey
Tanzania, Dar es Salaam
Muhimbili University of Health and Allied Sciences
Nyambo, Thomas B.
Tanzania, Dar es Salaam
Muhimbili University of Health and Allied Sciences
Omar, Sabah Ahmed
Kenya, Nairobi
Kenya Medical Research Institute
Wambebe, Charles O.
Nigeria, Abuja
International Biomedical Research in Africa
Ranciaro, Alessia
United States, Philadelphia
University of Pennsylvania
Hirbo, Jibril B.
United States, Philadelphia
University of Pennsylvania
Tishkoff, Sarah A.
United States, Philadelphia
University of Pennsylvania
Statistics
Citations: 53
Authors: 13
Affiliations: 7
Identifiers
Doi:
10.1016/j.ajhg.2011.05.005
ISSN:
00029297
e-ISSN:
15376605
Research Areas
Genetics And Genomics
Infectious Diseases
Study Design
Cross Sectional Study