Testing Wright's Intermediate Population Size Hypothesis - When Genetic Drift is a Good Thing

In his 1931 monograph, Sewall Wright predicted genetic drift would overwhelm selection in very small populations, and selection would dominate in large ones, but also concluded drift could facilitate selection in populations of intermediate size. The idea that drift and selection would act together in smaller populations has not been evaluated using analytical or numerical approaches even as empirical evidence of rapid evolution associated with population bottlenecks has continued to accumulate. I used forward-time simulations with random mating and discrete generations to test the hypothesis that drift can facilitate selection in small populations. I find evidence of drift facilitation of selection as increases in levels of{Delta} q in small populations (N<100) when selection is weak (s<0.2) and when allele frequencies are low (q<0.5). Fixation of beneficial mutations is accelerated by drift facilitation in small populations for recessive and codominant alleles, and less so for dominant alleles. Drift facilitation accelerated fixation of beneficial mutations in small populations compared to predictions from diffusion equations, while fixation time was longer than predicted in large populations. Drift facilitation increases the probability of fixation of new mutations in small populations. Accumulation of beneficial mutations (fixation flux) over several thousand generations was high in small populations and declined rapidly for large populations, which accumulated large amounts of standing genetic variation. Even though selection is more efficient in large populations, the increased time for allele replacement and lack of drift facilitation can result in substantially slower rates of adaptive evolution. Small populations were more susceptible to the accumulation of drift load, while larger populations maintained higher levels of segregation load. These results indicate that drift facilitation in small populations promotes purging of genetic load and accelerated fixation of beneficial mutations, and may account for the large number of observations of rapid adaptation during population bottlenecks. Impact Summary - After the recognition of Gregor Mendels contributions to our understanding of the inheritance of genetically-determined traits around 1900, there was confusion as to whether the type of variation Mendel studied could account for evolution by natural selection, as described by Charles Darwin. This controversy was resolved when three theoreticians (Ronald Fisher, Sewell Wright, and J.B.S. Haldane) published books that integrated Mendelian genetics with evolution. Their contributions (referred to as the Modern Synthesis), focused on evolutionary processes occurring within and among populations of a species, and established a mathematical foundation for our understanding of evolutionary biology. The mathematical models developed by the three architects of the modern synthesis, and those who followed, predicted that the effects of natural selection would be overwhelmed by random genetic changes (referred to as Genetic Drift) in small populations, and that genetic drift would be minimal, while selection would be most effective in large populations. Even though one of Wrights major conclusions was that genetic drift and selection would work together (Drift Facilitation) to promote adaptive evolution in intermediate-sized populations, this idea has been almost completely ignored since it was first introduced in 1931. In this study, I use simulations of evolution in natural populations to evaluate the potential for drift facilitation to promote evolution in small populations. My work largely confirms Wrights predictions; the removal of deleterious mutations and promotion of adaptive evolution are enhanced in population sizes ranging from about 10 to 100. These results indicate that our paradigm for our understanding of evolution within populations needs refinement to emphasize the importance of drift facilitation in small populations, and to recognize that periods of reduced population size are opportunities for enhanced levels of adaptive evolution. "In a population of intermediate size ... there is continual random shifting of gene frequencies ... which leads to a relatively rapid, continuing, irreversible, and largely fortuitous, but not degenerative series of changes, even under static conditions." Wright 1931, Page 157.