What's all the fuss about epistasis?

A worthy (so I believe) repost from my other blog.... [begin repost] Several years back David wrote about Sewall Wright's Shifting Balance Theory. If you know much about the history of mathematical genetics you know that R.A. Fisher and Wright's disputes over the importance of population substructure, genetic drift and the adaptive landscape was a simmering pot looming in the background of the emergence of the Modern Synthesis. One of the points that Fisher and Wright clashed over was the relative evolutionary importance of epistasis. I want to emphasize the evolutionary importance, because of course R.A. Fisher did not reject mechanistic epistasis as a background feature of a specie's genetic architecture, rather he was skeptical of its relevance as a driver of evolution. It was the average effect of a single allele against a genetic background which resulted in phenotypic adaptation according to Fisher. Each beneficial mutation would be driven by directional selection toward fixation, while the vast majority of mutations would be purified from the genetic background. In contrast, Wright conceived of an evolutionary landscape where epistatic interactions across loci would result in isolated adaptive peaks cordoned off by depressed regions of reduced fitness. This pluralistic scenario would result in balancing selection that would maintain more variation within the genetic background than in Fisher's model. Then in the late 1960s the Lewontin and Hubby papers reported such high levels of allozyme polymorphism that both the "Classical" (Fisher) and "Balancing" (Wright) schools of the Modern Synthesis were sent scrambling.^1 The elucidation of The Neutral Theory of gene substitution by Mootoo Kimura explained away the relative lack of fixation on the molecular level, heterozygosity and polymorphism were simply the transitory states of the dynamic system where neutral alleles were progressively substituted for each other by random walk genetic forces. Nevertheless, after reading Speciation my mind wandered back to the possibilities inherent in epistasis, coadapted gene complexes, supergenes and all the assorted detritus that remains after you remove Fisher's additive genetic effects. With my questions in hand I decided to dive into Epistasis and the Evolutionary Process