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Penn researchers show new evidence of genetic 'arms race' against malaria
Date:6/9/2011

ntified several single-nucleotide polymorphisms that are candidates for that signature."

Across the 15 population sets, the researchers focused on polymorphisms in a pair of genes that code for proteins called glycophorin A and glycophorin B. These proteins exist on the surface of red blood cells, and changes to their shape affect the ability of the parasite causing malaria to bind to them and to infect the cells.

There are, however, two conflicting theories of why changes to glycophorin shape influence rates of malaria. One theory suggests that glycophorin A acts as a decoy, making itself more attractive to binding so that pathogens don't infect more vulnerable cells. Another theory suggests that glycophorin A mutates so that malaria parasites can't bind at all.

The researchers observed differing patterns of natural selection acting on the different regions of the two genes. They noted an excess of genetic variation being maintained in the region of glycophorin A that plays a critical role of entry of the malaria parasite into the blood cell.

"This signature of selection was strongest in populations that have the highest exposure to malaria," Tishkoff said.

In addition, the researchers identified a novel protein variant at glycophorin B in several populations with high levels of malaria that may also be a target of natural selection.

Comparisons to chimpanzee and orangutan genomes showed that these mutations occurred after the human lineage split from these closely related primates. But a process known as "gene conversion," in which similar genes can acquire mutations from one another during cell division, complicates tracking the exact history of the mutation's spread.

"The genes for glycophorin A and B arose through gene duplication. They are more than 95 percent similar to each other on the sequence level," Ko said. "Because they are so similar, sequences of A might bind to B during recombin
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Contact: Evan Lerner
elerner@upenn.edu
215-573-6604
University of Pennsylvania
Source:Eurekalert

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