August 17, 2009

Malaria and GYPC selection in humans vs. other primates

Molecular Biology and Evolution, doi:10.1093/molbev/msp183

Molecular evolution of GYPC: Evidence for recent structural innovation and positive selection in humans

Jason A. Wilder et al.

Abstract

GYPC encodes two erythrocyte surface sialoglycoproteins in humans, glycophorin C and glycophorin D (GPC & GPD), via initiation of translation at two start codons on a single transcript. The malaria-causing parasite Plasmodium falciparum uses GPC as a means of invasion into the human red blood cell. Here we examine the molecular evolution of GYPC among the Hominoidea (Greater and Lesser Apes) and also the pattern of polymorphism at the locus in a global human sample. We find an excess of non-synonymous divergence among species that appears to be caused solely by accelerated evolution of GYPC in the human lineage. Moreover, we find that the ability of GYPC to encode both GPC and GPD is a uniquely human trait, caused by the evolution of the GPC start codon in the human lineage. The pattern of polymorphism among humans is consistent with a hitchhiking event at the locus, suggesting that positive natural selection affected GYPC in the relatively recent past. Because GPC is exploited by P. falciparum for invasion of the red blood cell, we hypothesize that selection for evasion of P. falciparum has caused accelerated evolution of GYPC in humans (relative to other primates), and that this positive selection has continued to act in the recent evolution of our species. These data suggest that malaria has played a powerful role in shaping molecules on the surface of the human red blood cell. In addition, our examination of GYPC reveals a novel mechanism of protein evolution: co-option of UTR sequence following the formation of a new start codon. In the case of human GYPC the ancestral protein (GPD) continues to be produced through leaky translation. Because leaky translation is a widespread phenomenon among genes and organisms, we suggest that co-option of UTR sequence may be an important source of protein innovation.

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