Saturday, July 15, 2006

Malarial Resistance in Chimps vs. Humans

In this paper, the authors examine whether the variation and LD found in human G6PD is also evident in other primates, and conclude that humans responded to the malarial selection pressure differently than chimpanzees.

Contrasting Histories of G6PD Molecular Evolution and Malarial Resistance in Humans and Chimpanzees

Brian C. Verrelli, Sarah A. Tishkoff, Anne C. Stone and Jeffrey W. Touchman

Molecular Biology and Evolution, 23(8), 1592-1601. 2006

Abstract: Although mutations in the glucose-6-phosphate dehydrogenase (G6PD) gene result in several blood-related diseases in humans, they also confer resistance to malarial infection. This association between G6PD and malaria was supported by population genetic analyses of the G6PD locus, which indicated that these mutations may have recently risen in frequency in certain geographic regions as a result of positive selection. Here we characterize nucleotide sequence variation in a 5.2-kb region of the G6PD locus in a population sample of 56 chimpanzees, as well as among 7 other nonhuman primates, to compare with that in humans in determining whether other primates that are impacted by malaria also exhibit patterns of G6PD polymorphism or divergence consistent with positive selection. We find that chimpanzees have several amino acid variants but that the overall pattern at G6PD in chimpanzees, as well as in Old and New World primates in general, can be explained by recent purifying selection as well as strong functional constraint dating back to at least 30–40 MYA. These comparative analyses suggest that the recent signature of positive selection at G6PD in humans is unique.

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