title: Stepwise modification of a modular enhancer underlies adaptation in a Drosophila population.
abstract: The evolution of cis regulatory elements (enhancers) of developmentally regulated genes plays a large role in the evolution of animal morphology. However, the mutational path of enhancer evolution--the number, origin, effect, and order of mutations that alter enhancer function--has not been elucidated. Here, we localized a suite of substitutions in a modular enhancer of the ebony locus responsible for adaptive melanism in a Ugandan Drosophila population. We show that at least five mutations with varied effects arose recently from a combination of standing variation and new mutations and combined to create an allele of large phenotypic effect. We underscore how enhancers are distinct macromolecular entities, subject to fundamentally different, and generally more relaxed, functional constraints relative to protein sequences.
authors.affiliation: Howard Hughes Medical Institute and Laboratory of Molecular Biology, University of Wisconsin, Madison, WI 53706, USA.
authors.forename: Mark
authors.initials: M
authors.lastname: Rebeiz
authors.forename: John E
authors.initials: JE
authors.lastname: Pool
authors.forename: Victoria A
authors.initials: VA
authors.lastname: Kassner
authors.forename: Charles F
authors.initials: CF
authors.lastname: Aquadro
authors.forename: Sean B
authors.initials: SB
authors.lastname: Carroll
mesh_terms: D000005:Abdomen; D000220:Adaptation, Biological; D000483:Alleles; D000818:Animals; D030801:Animals, Genetically Modified; D005075:Biological Evolution; D004268:DNA-Binding Proteins / Q000235:genetics*; D029721:Drosophila Proteins / Q000235:genetics*; D004331:Drosophila melanogaster / Q000235:genetics* / Q000254:growth & development / Q000502:physiology; D004742:Enhancer Elements, Genetic; D019143:Evolution, Molecular; D018507:Gene Expression Regulation, Developmental; D006239:Haplotypes; D008969:Molecular Sequence Data; D009154:Mutation; D010858:Pigmentation / Q000235:genetics*; D011110:Polymorphism, Genetic; D014454:Uganda
chemical_list: D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; C116191:e protein, Drosophila