Research Articles

Balancing selection is a mode of adaptation that leads to the persistence of variation in a population or species in the face of stochastic loss by genetic drift. In humans, examples include the sickle cell hemoglobin polymorphism, maintained by heterozygote advantage in environments in which Plasmodium falciparum is endemic, as well as other cases that likely arose recently in evolution in response to malaria (1). Beyond humans, examples of balancing selection are known in a wide range of organisms and often seem to arise from predator-prey or host-pathogen interactions (e.g., (2–8)). Most are not thought to be due to heterozygote advantage but to negative frequency dependent selection, as occurs at self-incompatibility loci in plants (5, 9), or to temporally or spatially varying selection, as seen, for example, at R genes in Arabidopsis (4). The genetic basis is known only in a small subset of cases, however, and the age-old question (10–12) of how much genetic variation is main-tained by balancing selection remains largely open