Theory suggests that the variance-to-mean ratio in the number of nucleotide substitutions which accumulate on replicate lineages in a gene can give good insight into the action of natural selection on the locus. The Dispersion Index (R) is defined as this ratio, but published estimates of R come exclusively from metazoans and have been confounded by a number of factors, weakening the conclusions of these studies. Chief among these factors is the failure of diverging metazoan species to be truly controlled replicates of one another, as they naturally differ historically in many (unknowable) ecological and evolutionary respects. The goal of this project is to measure the Dispersion Index at all 13 protein-coding loci in laboratory populations of the bacteriophage phi6. The bacteriophage's short generation time and high mutation rate will permit the rapid accumulation of substitutions in truly replicate populations. Theory suggests that R may be sensitive to functional constraint and to population size; both of these predictions will be tested. From a clinical perspective, understanding the basis of rate variation is important because RNA viruses are pathogens. If the emergence of a new virus or the escape of one from a vaccine is facilitated by rapid evolution, it would be useful to know what factors, e.g. small or large populations, facilitate this process.
|Weinreich, Daniel M; Knies, Jennifer L (2013) Fisher's geometric model of adaptation meets the functional synthesis: data on pairwise epistasis for fitness yields insights into the shape and size of phenotype space. Evolution 67:2957-72|