Fisher, Wright & dominance

A few months ago I was posting on R.A. Fisher's Genetical Theory of Natural Selection. I stopped because I was a bit confused as to what to do about the chapter on dominance, which was basically an exposition on a theory which has been falsified by the preponderance of data. In sum, R.A. Fisher contended that the dominance of an allele emerged via evolutionary processes, while his primary interlocutor Sewall Wright contended that this phenomenon was an emergent property of physiological dynamics. Fisher noted that "Wild Type" phenotypes are invariably dominant. He suggested that deleterious mutants are initially semi-dominant and so reduce fitness in heterozygotes, but modifier alleles on other loci arose in response to selection to mask their phenotypic effect. So, over time a mutant allele would manifest recessiveness where the trait would only emerge in the non-heterozygote state (which is very rare because these alleles were generally extant at low frequency). Wright's explanation was more straightforward: a biochemical process may require only a threshold of protein product, and so one copy of the allele may be sufficient to result in function. The reality is that on many traits there is a discernible difference between Wild Type homozygotes and heterozygotes, but to the first approximation this is not evident. But in any case, the fact that the latter explanation is what most students of biology are taught attests to the fact that the elucidation of molecular mechanisms in genetics over the past few generations has resulted in the vindication in general of Wright's hypothesis. But there is a bigger philosophical difference at work here I believe. Fisher was at heart a theoretician who applied his sharp mathematical mind to biological questions. Wright was originally an experimentalist, an applied researcher in physiological genetics, who became interested in abstract questions later because he wished to model the systems of breeding within which he worked. This difference in background led to a parting of the ways in regards to the manner in which the two great theoretical minds in population genetics viewed the various forces in evolutionary dynamics. Fisher was the arch-selectionist, and his explanation of the origin of dominance highlights his general recourse to the overarching logic of selectionist processes in shaping genetic architecture and phenotypic expression. In contrast, Wright was originally a physiological geneticist (in our day he would likely have started out a molecular geneticist) who was more conscious of the proximate processes which constrained and counteracted the force of natural selection. Given an infinite amount of time the inefficiencies of mechanistic dominance might be abolished by the emergence of modifier genes, but the reality is that by that time the species and populations in question would likely be at another peak of metastability. In regards to the question of dominance we have here an illustration of the weakness of Fisher's tendency to focus on grand ultimate processes at the expense of minute details of implementation. Related: Robert Skipper has a post which addresses this controversy between Fisher & Wright in more detail.