Immunology

Maintaining Diversity

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Science  03 Jul 2009:
Vol. 325, Issue 5936, pp. 12-13
DOI: 10.1126/science.325_12d

Exposure to infectious agents has exerted selective pressure on the evolution of one group of immune system genes. The hygiene hypothesis, proposed two decades ago, posits that the reduced exposure of inhabitants of modern industrialized societies to microbes and macropathogens (such as parasitic worms) has increased susceptibility to inflammatory conditions such as allergies and autoimmune disease. Taking a population genetics approach, Fumagalli et al. investigated how infectious agents have affected the genetic variability of interleukins, which are critical signaling molecules of the immune system, and their associated receptors. They found that pathogen richness, a measure of pathogen diversity in a specific geographic area, has driven the selection of several interleukin family genes; in particular, balanced selection, a type of selection that maintains genetic variation within populations and is unusual in humans, has contributed to the evolution of five interleukin genes. Finally, the authors demonstrated that six of the nine known risk alleles associated with inflammatory conditions such as celiac disease and Crohn's disease correlated with pathogen richness, but in contrast to the hygiene hypothesis, more so with bacteria, viruses, and fungi rather than worms. Hence, pathogen-influenced evolution is a double-edged sword: The same bugs that helped us to develop an immune response to a wide array of pathogens also may have contributed to the appearance of debilitating inflammatory diseases.

J. Exp. Med. 206, 1395 (2009).

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