Tempo and mode of regulatory evolution in Drosophila

Joseph D Coolon,C Joel Mcmanus,Brenton R Graveley,Kraig R Stevenson,Patricia J Wittkopp

doi:10.1101/gr.163014.113

Abstract

Genetic changes affecting gene expression contribute to phenotypic divergence; thus, understanding how regulatory networks controlling gene expression change over time is critical for understanding evolution. Prior studies of expression differences within and between species have identified properties of regulatory divergence, but technical and biological differences among these studies make it difficult to assess the generality of these properties or to understand how regulatory changes accumulate with divergence time. Here, we address these issues by comparing gene expression among strains and species of Drosophila with a range of divergence times and use F1 hybrids to examine inheritance patterns and disentangle cis- and trans-regulatory changes. We find that the fixation of compensatory changes has caused the regulation of gene expression to diverge more rapidly than gene expression itself. Specifically, we observed that the proportion of genes with evidence of cis-regulatory divergence has increased more rapidly with divergence time than the proportion of genes with evidence of expression differences. Surprisingly, the amount of expression divergence explained by cis-regulatory changes did not increase steadily with divergence time, as was previously proposed. Rather, one species (Drosophila sechellia) showed an excess of cis-regulatory divergence that we argue most likely resulted from positive selection in this lineage. Taken together, this work reveals not only the rate at which gene expression evolves, but also the molecular and evolutionary mechanisms responsible for this evolution.

Highlights

Understanding the relationship between tempo and mode is essential for understanding the evolutionary process (Simpson 1944)
This approach was initially used to separate cis- and transregulatory effects of divergence affecting expression of dozens of genes. These studies suggested that (1) cis-regulatory changes are more common than trans-regulatory changes between species (Wittkopp et al 2004); (2) genes with cis- and trans-acting changes favoring expression of opposite alleles are more likely than other types of changes to cause misexpression in F1 hybrids (Landry et al 2005); (3) environmental factors modulate relative cis-regulatory activity; (4) cis-regulatory variation is abundant in natural populations (Osada et al 2006; Genissel et al 2007; Campbell et al 2008; Gruber and Long 2009); and (5) the amount of expression divergence attributable to cis-acting changes is greater between than within species (Wittkopp et al 2008)
Sequence divergence observed in transcribed regions of these strains correlated with published estimates of divergence time (Fig. 1C) as well as the number of RNA-seq reads informative for allele-specific expression (Fig. 1D)

Summary

Introduction

Understanding the relationship between tempo (the rate at which a trait evolves) and mode (the manner in which a trait evolves) is essential for understanding the evolutionary process (Simpson 1944). The net effects of interactions among divergent regulatory alleles are revealed by comparing levels of total expression in F1 hybrids to parental genotypes This approach was initially used to separate cis- and transregulatory effects of divergence affecting expression of dozens of genes. These studies suggested that (1) cis-regulatory changes are more common than trans-regulatory changes between species (Wittkopp et al 2004); (2) genes with cis- and trans-acting changes favoring expression of opposite alleles are more likely than other types of changes to cause misexpression in F1 hybrids (Landry et al 2005); (3) environmental factors modulate relative cis-regulatory activity (de Meaux et al 2006); (4) cis-regulatory variation is abundant in natural populations (Osada et al 2006; Genissel et al 2007; Campbell et al 2008; Gruber and Long 2009); and (5) the amount of expression divergence attributable to cis-acting changes is greater between than within species (Wittkopp et al 2008).

Methods

Results

Conclusion