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PMID: 11861881 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Natural selection on the erythrocyte surface.

Molecular biology and evolution ·Vol. 19 ·No. 3 ·2002-03-00 ·Pages 223-9

Baum J, Ward RH, Conway DJ

Abstract

Surface glycoproteins are principal receptors used by pathogens to invade target cells. It has been suggested that mammalian erythrocyte surface glycoproteins function as decoy receptors attracting pathogens to the anucleated erythrocyte and away from their target tissues. Glycophorin A (GYPA) is solely expressed on the erythrocyte surface where it is the most abundant sialoglycoprotein, although its function is unknown. The pathogen decoy hypothesis may be relevant here, as GYPA has been shown in vitro to bind numerous viruses and bacteria, which do not infect erythrocytes. However, it is also a receptor for erythrocyte invasion by the malarial parasite Plasmodium falciparum. Analyses of gypa sequence variation among six higher primates and within a human population show that there is a large excess of replacement (nonsynonymous) substitutions along each primate lineage (particularly on exons 2-4 encoding the extracellular glycosylated domain of GYPA) and a significant excess of polymorphisms in exon 2 (encoding the terminal portion of the extracellular domain) within humans. These two signatures suggest that there has been exceptionally strong positive selection on this receptor driving GYPA divergence during primate evolution and balancing selection maintaining allelic variation within human populations. The pathogen decoy hypothesis alone is adequate to explain both these signatures of between-species and within-species diversifying selection. This has implications for understanding the functions of erythrocyte surface components and their roles in health and disease.

MeSH Terms

Alleles Amino Acid Sequence Animals Base Sequence Conserved Sequence Erythrocytes/metabolism Glycophorins/genetics,metabolism Humans Membrane Glycoproteins/genetics,metabolism Molecular Sequence Data Polymorphism, Genetic/genetics Primates/genetics Protein Structure, Tertiary/genetics Selection, Genetic Sequence Homology

Chemicals

Glycophorins Membrane Glycoproteins

Authors & Affiliations

3 authors, click to expand affiliations / ORCID

Baum Jake

Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine. Institute of Biological Anthropology, University of Oxford. [email protected]

Ward Ryk H

Conway David J

Article Info

Journal

Molecular biology and evolution

Abbr.

Mol Biol Evol

ISSN

0737-4038

DOI

10.1093/oxfordjournals.molbev.a004075

[email protected]

Published

2002-03-00

Pages

223-9

Language

English

Region

United States

NLM ID

8501455

Subset

Databases

GENBANK

AJ309706, AJ309708, AJ309828, AJ309829, AJ309830, AJ309831, AJ309832, AJ309833, AJ309834, AJ309835, AJ309836, AJ309837, AJ309838, AJ309839, AJ309840, AJ309841, AJ309842, AJ309843, AJ309844, AJ309845, AJ311318, AJ311319, AJ311320, AJ311321, AJ311322, AJ311323, AJ311324, AJ311325, AJ311326, AJ311327, AJ311328, AJ311329, AJ311330, AJ311331, AJ311332

External Links

PubMed source DOI: 10.1093/oxfordjournals.molbev.a004075 View journal details

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Natural selection on the erythrocyte surface.

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