Adaptive gene expression divergence inferred from population genomics

Abstract

Detailed studies of individual genes have shown that gene expression divergence often results from adaptive evolution of regulatory sequence. Genome-wide analyses, however, have yet to unite patterns of gene expression with polymorphism and divergence to infer population genetic mechanisms underlying expression evolution. Here, we combined genomic expression data--analyzed in a phylogenetic context--with whole genome light-shotgun sequence data from six Drosophila simulans lines and reference sequences from D. melanogaster and D. yakuba. These data allowed us to use molecular population genetics to test for neutral versus adaptive gene expression divergence on a genomic scale. We identified recent and recurrent adaptive evolution along the D. simulans lineage by contrasting sequence polymorphism within D. simulans to divergence from D. melanogaster and D. yakuba. Genes that evolved higher levels of expression in D. simulans have experienced adaptive evolution of the associated 3' flanking and amino acid sequence. Concomitantly, these genes are also decelerating in their rates of protein evolution, which is in agreement with the finding that highly expressed genes evolve slowly. Interestingly, adaptive evolution in 5' cis-regulatory regions did not correspond strongly with expression evolution. Our results provide a genomic view of the intimate link between selection acting on a phenotype and associated genic evolution.

Figure 1. D. simulans Heterozygosity (Left) and Divergence (Right) for Genes with and without Gene Expression Divergence

Divergent gene expression is associated with rapid evolution of protein coding and regulatory regions. There is no relationship between heterozygosity and expression divergence. Points are means with standard error. See Table S2 for sample sizes. NC, no change; ↑, increase in expression along the D. simulans lineage; ↓, decrease in expression along the D. simulans lineage.

Figure 2. Proportion of Genes Evolving Adaptively in Each Expression Category and for Each Feature

Genes with increased expression levels have associated recurrent adaptive evolution of 3′ UTR and 3′ flanking regions as well as evidence for recent adaptive evolution of protein coding regions. For resampling tests, *p < 0.05 and **p < 0.01. Descriptions of tests for recurrent and recent adaptive evolution can be found in the Materials and Methods section.