title: Morphological evolution caused by many subtle-effect substitutions in regulatory DNA.
abstract: Morphology evolves often through changes in developmental genes, but the causal mutations, and their effects, remain largely unknown. The evolution of naked cuticle on larvae of Drosophila sechellia resulted from changes in five transcriptional enhancers of shavenbaby (svb), a transcript of the ovo locus that encodes a transcription factor that governs morphogenesis of microtrichiae, hereafter called 'trichomes'. Here we show that the function of one of these enhancers evolved through multiple single-nucleotide substitutions that altered both the timing and level of svb expression. The consequences of these nucleotide substitutions on larval morphology were quantified with a novel functional assay. We found that each substitution had a relatively small phenotypic effect, and that many nucleotide changes account for this large morphological difference. In addition, we observed that the substitutions had non-additive effects. These data provide unprecedented resolution of the phenotypic effects of substitutions and show how individual nucleotide changes in a transcriptional enhancer have caused morphological evolution.
authors: Howard Hughes Medical Institute and Department of Ecology and Evolutionary Biology, Princeton University, Princeton, New Jersey 08544, USA.
authors: Nicolás
authors: N
authors: Frankel
authors: Deniz F
authors: DF
authors: Erezyilmaz
authors: Alistair P
authors: AP
authors: McGregor
authors: Shu
authors: S
authors: Wang
authors: François
authors: F
authors: Payre
authors: David L
authors: DL
authors: Stern
mesh_terms: D000818:Animals; D001483:Base Sequence; D005075:Biological Evolution; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D004330:Drosophila / Q000033:anatomy & histology* / Q000196:embryology / Q000235:genetics*; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism; D004331:Drosophila melanogaster / Q000033:anatomy & histology / Q000196:embryology / Q000235:genetics; D004625:Embryo, Nonmammalian; D004742:Enhancer Elements, Genetic / Q000235:genetics*; D005260:Female; D018507:Gene Expression Regulation, Developmental; D007814:Larva; D008297:Male; D010641:Phenotype; D016415:Sequence Alignment; D012689:Sequence Homology, Nucleic Acid; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D014157:Transcription Factors; C089512:ovo protein, Drosophila