Allele frequency divergence reveals ubiquitous influence of positive selection in Drosophila

Abstract

Resolving the role of natural selection is a basic objective of evolutionary biology. It is generally difficult to detect the influence of selection because ubiquitous non-selective stochastic change in allele frequencies (genetic drift) degrades evidence of selection. As a result, selection scans typically only identify genomic regions that have undergone episodes of intense selection. Yet it seems likely such episodes are the exception; the norm is more likely to involve subtle, concurrent selective changes at a large number of loci. We develop a new theoretical approach that uncovers a previously undocumented genome-wide signature of selection in the collective divergence of allele frequencies over time. Applying our approach to temporally resolved allele frequency measurements from laboratory and wild Drosophila populations, we quantify the selective contribution to allele frequency divergence and find that selection has substantial effects on much of the genome. We further quantify the magnitude of the total selection coefficient (a measure of the combined effects of direct and linked selection) at a typical polymorphic locus, and find this to be large (of order 1%) even though most mutations are not directly under selection. We find that selective allele frequency divergence is substantial at intermediate allele frequencies, which we argue is most parsimoniously explained by positive -- not purifying -- selection. Thus, in these populations most mutations are far from evolving neutrally in the short term (tens of generations), including mutations with neutral fitness effects, and the result cannot be explained simply as a purging of deleterious mutations. Author summaryNatural selection is the process fundamentally driving evolutionary adaptation; yet the specifics of how natural selection molds the genome are contentious. A prevailing neutralist view holds that the evolution of most mutations is essentially random. Here, we develop new theory that looks past the stochasticity of individual mutations and instead analyzes the behavior of mutations across the genome as a collective. We find that selection has a strong non-random influence on most of the Drosophila genome over short timescales (tens of generations), including the bulk of mutations that are not themselves directly targeted by selection. We show that this likely involves ongoing positive selection.