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Pathogens shape evolution of humans' most diverse genes

The great physical diversity that evolution has forged in human beings is in evidence wherever we look, but the genes exhibiting the greatest diversity at the DNA level happen to function in a wholly invisible process: immunity. Genes encoding the Human Leukocyte Antigen (HLA) proteins are among the most diverse in the human genome, and scientists have proposed a number of hypotheses to explain why. This week, researchers report new findings that support the idea that the striking diversity of HLA genotypes in humans is shaped to a significant degree by the different sets of pathogenic species encountered by different human populations around the world.

The findings are reported in the June 7 issue of Current Biology by Dr. Franck Prugnolle and colleagues at the University of Cambridge.

HLA class I proteins are critical players in the recognition of antigens--bits of foreign protein derived from invading pathogens--and in the presentation of the antigens on the surfaces of cells. HLA proteins and the antigens they present are recognized by specialized immune cells, resulting in immune responses that combat disease. But why should HLA genes be so diverse? Numerous factors could contribute, but a leading idea has been that pathogens themselves play a role. Past work had offered clues to this effect--for example, individuals with some HLA genotypes are more susceptible (or more resistant) to some pathogens than others. If different versions of HLA proteins can influence how the immune system deals with a particular pathogen, it follows that, in theory, HLA genes should evolve to deal most effectively with the various antigens humans encounter.

This kind of evolution, leading to diverse HLA genotypes in which individuals possess two different versions, or alleles, of the various HLA genes, forms the basis for the idea of "pathogen-driven balancing selection," or PDBS.

In their new work, the researchers set out to test the PDBS hypothesi
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Contact: Heidi Hardman
hhardman@cell.com
1-617-397-2879
Cell Press
6-Jun-2005


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