Abstract
During human evolution, genetic adaptation to local pathogenic load has been a major force shaping genome variability due to the huge burden that infective agents have exerted through history. Signatures of pathogen-driven selection have been observed in many immune-related genes, including loci involved in the innate immune response. Natural selection on the immune system tends to favor the maintenance of genetic variability through the action of balancing selection, as it allows an efficient immune response to a wide range of pathogenic agents. Some of the known variants conferring protection to infective agents have been shown to carry signals of past natural selection. In the case of autoimmune disorders, pathogen-driven selection maintains common alleles that confer resistance to the infectious disease, presumably as a result of adaptation to high pathogen burden in the past, in line with the hygiene hypothesis. With the increasing availability of genetic and phenotypic data, population genetic studies will help elucidate the mechanisms underlying human evolutionary adaptation to pathogens and prove useful in a field where traditional association studies with high statistical power have been difficult to implement.
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