The phenomenon of dominance and its meaning accompanied the science of genetics from its initiation. Bateson interpreted it in terms of the Presence and Absence Hypothesis. R. A. Fisher, taking notice of the harmful effects of inbreeding, pointed out that “if we assume that adaptation is the result of selection, the majority of large mutations must be harmful” (Fisher, 1922, 323). Thus a major task of the evolution of dominance would be to equalize the phenotypes of the heterozygotes to that of the homozygote for the wild-type allele (Fisher, 1928). However, doubts were raised about the efficiency of natural selection in carrying out the task (Wright, 1929a). According to Wright's theory of the functional organization of the cell that related the genotype to the phenotype, dominance would be the outcome of interaction:

Haldane (1930) and Muller (1932), following Shull (1909, 415) and Wright, suggested that the amount of product produced by the alleles of a gene varied asymptotically, and that the wild-type alleles in diploids have been selected to function in the relatively saturated segment of the asymptotic gene/product curve (see Chapter 14).