Allen Orr and the genetics of adaptation.

Over most of the 20th century, evolutionary biologists predominantly subscribed to a strong form of "micro-mutationism," in which adaptive phenotypic divergence arises from allele frequency changes at many loci, each with a small effect on the phenotype. To be sure, there were well-known examples of large-effect alleles contributing to adaptation, yet such cases were generally regarded as atypical and unrepresentative of evolutionary change in general. In 1998, Allen Orr published a landmark theoretical paper in Evolution, which showed that both small- and large-effect mutations are likely to contribute to "adaptive walks" of a population to an optimum. Coupled with a growing set of empirical examples of large-effect alleles contributing to divergence (e.g., from QTL studies), Orr's paper provided a mathematical formalism that converted many evolutionary biologists from micro-mutationism to a more pluralistic perspective on the genetic basis of evolutionary change. We revisit the theoretical insights emerging from Orr's paper within the historical context leading up to 1998, and track the influence of this paper on the field of evolutionary biology through an examination of its citations over the last two decades and an analysis of the extensive body of theoretical and empirical research that Orr's pioneering paper inspired.