The heat-shock response and the molecular basis of genetic dominance

Wild-type alleles are usually dominant over deleterious mutant alleles. For a particular pair of such alleles possible populations include a wild-type homozygote population, a heterozygote population, and a mutant homozygote population. Fisher's theory that dominance would evolve by selection acting on the heterozygote subpopulation has lost ground in favour of the "dose-response" theory under which dominance is an incidental consequence of selection acting on the wild-type homozygote population. This postulates a "margin of safety" in the quantity of wild-type gene product so that heterozygotes with only one copy of a wild-type allele still have sufficient product for normal function. The selective force postulated to lead to the evolution of this margin of safety is some unspecified "extreme environment disturbance". The author has proposed elsewhere that the heat-shock response evolved very early as part of an intracellular system for self/not-self discrimination. This paper proposes that the rapid decrease in quantity of most normal proteins occurring in the heat-shock response would have provided a sufficient selective force for the margin of safety to have evolved.