title: Enhancer Runaway and the Evolution of Diploid Gene Expression.
abstract: Evidence is mounting that the evolution of gene expression plays a major role in adaptation and speciation. Understanding the evolution of gene regulatory regions is indeed an essential step in linking genotypes and phenotypes and in understanding the molecular mechanisms underlying evolutionary change. The common view is that expression traits (protein folding, expression timing, tissue localization and concentration) are under natural selection at the individual level. Here, we use a theoretical approach to show that, in addition, in diploid organisms, enhancer strength (i.e., the ability of enhancers to activate transcription) may increase in a runaway process due to competition for expression between homologous enhancer alleles. These alleles may be viewed as self-promoting genetic elements, as they spread without conferring a benefit at the individual level. They gain a selective advantage by getting associated to better genetic backgrounds: deleterious mutations are more efficiently purged when linked to stronger enhancers. This process, which has been entirely overlooked so far, may help understand the observed overrepresentation of cis-acting regulatory changes in between-species phenotypic differences, and sheds a new light on investigating the contribution of gene expression evolution to adaptation.
authors.affiliation: UMR 5175 CEFE, CNRS, Université Montpellier, Université P. Valéry, EPHE, Montpellier, France.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Fyon
authors.affiliation: UMR 5175 CEFE, CNRS, Université Montpellier, Université P. Valéry, EPHE, Montpellier, France.
authors.forename: Aurélie
authors.initials: A
authors.lastname: Cailleau
authors.affiliation: UMR 5175 CEFE, CNRS, Université Montpellier, Université P. Valéry, EPHE, Montpellier, France.
authors.forename: Thomas
authors.initials: T
authors.lastname: Lenormand
mesh_terms: D000483:Alleles; D000818:Animals; D004171:Diploidy; D004742:Enhancer Elements, Genetic; D019143:Evolution, Molecular; D005786:Gene Expression Regulation; D008962:Models, Theoretical; D012641:Selection, Genetic / Q000235:genetics*; D017384:Sequence Deletion