Quantifying Selection Acting on a Complex Trait Using Allele Frequency Time Series Data

When selection is acting on a large genetically diverse population, beneficial alleles increase in frequency. This fact can be used to map quantitative trait loci by sequencing the pooled DNA from the population at consecutive time points and observing allele frequency changes. Here, we present a population genetic method to analyze time series data of allele fre-quencies from such an experiment. Beginning with a range of proposed evolutionary scenarios, the method measures the consistency of each with the observed frequency changes. Evolutionary theory is utilized to formulate equations of motion for the allele frequencies, following which likelihoods for having observed the sequencing data under each scenario are de-rived. Comparison of these likelihoods gives an insight into the prevailing dynamics of the system under study. We illus-trate the method by quantifying selective effects from an experiment, in which two phenotypically different yeast strains were first crossed and then propagated under heat stress (Parts L, Cubillos FA, Warringer J, et al. [14 co-authors]. 2011. Re-vealing the genetic structure of a trait by sequencing a population under selection. Genome Res). From these data, we dis-cover that about 6 % of polymorphic sites evolve nonneutrally under heat stress conditions, either because of their link-age to beneficial (driver) alleles or because they are drivers themselves. We further identify 44 genomic regions contain-ing one or more candidate driver alleles, quantify their apparent selective advantage, obtain estimates of recombination rates within the regions, and show that the dynamics of the drivers display a strong signature of selection going be-yond additive models. Our approach is applicable to study adaptation in a range of systems under different evolutionary pressures. Key words: adaptive molecular evolution, fitness effects of mutations, artificial selection