Natural selection and infectious disease in human populations

Abstract

Infectious pathogens are among the strongest selective forces that shape the human genome. Migrations and cultural changes in the past 100,000 years exposed populations to dangerous new pathogens.Host genetics influences susceptibility to infectious disease. Evolutionary adaptations for resistance and symbiosis may underlie common immune-mediated diseases.Signatures of selection and methods to detect them vary with the age, geographical spread and virulence of the pathogen.A history of selection on a trait adds power to association studies by driving the emergence of common alleles of strong effect. Combining selection and association metrics can further increase power.Genome-wide association studies (GWASs) of susceptibility to pathogens that are moderately old (1,000–50,000 years ago), geographically limited in history and exerted strong positive selective pressure will have the most power if GWASs can be done in the historically affected population.An understanding of host–pathogen interactions can inform the development of new therapies for both infectious diseases and common immune-mediated diseases. Supplementary information The online version of this article (doi:10.1038/nrg3734) contains supplementary material, which is available to authorized users.