title: Molecular Mechanisms and Evolutionary Processes Contributing to Accelerated Divergence of Gene Expression on the Drosophila X Chromosome.
abstract: In species with a heterogametic sex, population genetics theory predicts that DNA sequences on the X chromosome can evolve faster than comparable sequences on autosomes. Both neutral and nonneutral evolutionary processes can generate this pattern. Complex traits like gene expression are not predicted to have accelerated evolution by these theories, yet a "faster-X" pattern of gene expression divergence has recently been reported for both Drosophila and mammals. Here, we test the hypothesis that accelerated adaptive evolution of cis-regulatory sequences on the X chromosome is responsible for this pattern by comparing the relative contributions of cis- and trans-regulatory changes to patterns of faster-X expression divergence observed between strains and species of Drosophila with a range of divergence times. We find support for this hypothesis, especially among male-biased genes, when comparing different species. However, we also find evidence that trans-regulatory differences contribute to a faster-X pattern of expression divergence both within and between species. This contribution is surprising because trans-acting regulators of X-linked genes are generally assumed to be randomly distributed throughout the genome. We found, however, that X-linked transcription factors appear to preferentially regulate expression of X-linked genes, providing a potential mechanistic explanation for this result. The contribution of trans-regulatory variation to faster-X expression divergence was larger within than between species, suggesting that it is more likely to result from neutral processes than positive selection. These data show how accelerated evolution of both coding and noncoding sequences on the X chromosome can lead to accelerated expression divergence on the X chromosome relative to autosomes.
authors.affiliation: Department of Ecology and Evolutionary Biology, University of Michigan jcoolon@wesleyan.edu wittkopp@umich.edu.
authors.forename: Joseph D
authors.initials: JD
authors.lastname: Coolon
authors.affiliation: Department of Computational Medicine and Bioinformatics, University of Michigan.
authors.forename: Kraig R
authors.initials: KR
authors.lastname: Stevenson
authors.affiliation: Department of Biological Sciences, Carnegie Mellon University Department of Genetics and Developmental Biology, Institute for Systems Genomics, University of Connecticut Health Center.
authors.forename: C Joel
authors.initials: CJ
authors.lastname: McManus
authors.affiliation: Department of Molecular, Cellular, and Developmental Biology, University of Michigan.
authors.forename: Bing
authors.initials: B
authors.lastname: Yang
authors.affiliation: Department of Genetics and Developmental Biology, Institute for Systems Genomics, University of Connecticut Health Center.
authors.forename: Brenton R
authors.initials: BR
authors.lastname: Graveley
authors.affiliation: Department of Ecology and Evolutionary Biology, University of Michigan Department of Computational Medicine and Bioinformatics, University of Michigan Department of Molecular, Cellular, and Developmental Biology, University of Michigan jcoolon@wesleyan.edu wittkopp@umich.edu.
authors.forename: Patricia J
authors.initials: PJ
authors.lastname: Wittkopp
mesh_terms: D000818:Animals; D001483:Base Sequence; D005075:Biological Evolution; D004331:Drosophila melanogaster / Q000235:genetics*; D005260:Female; D005786:Gene Expression Regulation; D050172:Genes, X-Linked; D014644:Genetic Variation; D008297:Male; D012045:Regulatory Sequences, Nucleic Acid / Q000235:genetics; D014157:Transcription Factors / Q000378:metabolism; D014960:X Chromosome / Q000235:genetics*
chemical_list: D014157:Transcription Factors
keywords: cis-regulation; faster-X; gene expression; selection; trans-regulation