Scientific Contribution Why disease persists: an evolutionary nosology

Although natural selection might be expected to reduce the incidence and severity of disease, disease persists. Natural selection leads to increases in the mean fitness of populations and so will reduce the frequency of disease-associated alleles, but other evolutionary processes, such as mutation and gene flow, may introduce or increase the frequency of these deleterious alleles. The pleiotropic actions of genes and the epistatic interactions between them complicate the relationship between genotype and phenotype, and may result in the preservation of disease-associated alleles. Deleterious alleles may also be maintained because of linkage to beneficial alleles. The inability of natural selection to eliminate diseases of aging is a reminder that fitness success in producing progeny, or in contributing genes to the population gene pool is not equivalent to the absence of disease. Nutritional or psychosocial cues may lead to life history strategies that maximize survival to reproductive maturity at the expense of disease later in life. Natural selection acts on genes, cells, and groups, as well as on organisms; the outcome of evolution reflects selection at different levels of biological organization. Finally, the human environment is constantly changing, largely because of the evolution of our parasites and because of changes in cultural beliefs and practices; genetic evolution is comparatively slow and lags behind environmental change. An evolutionary nosology complements traditional medical nosologies and enhances our understanding of the persistence of disease and the meaning of human variation.