title: Epistatic and combinatorial effects of pigmentary gene mutations in the domestic pigeon.
abstract: Understanding the molecular basis of phenotypic diversity is a critical challenge in biology, yet we know little about the mechanistic effects of different mutations and epistatic relationships among loci that contribute to complex traits. Pigmentation genetics offers a powerful model for identifying mutations underlying diversity and for determining how additional complexity emerges from interactions among loci. Centuries of artificial selection in domestic rock pigeons (Columba livia) have cultivated tremendous variation in plumage pigmentation through the combined effects of dozens of loci. The dominance and epistatic hierarchies of key loci governing this diversity are known through classical genetic studies, but their molecular identities and the mechanisms of their genetic interactions remain unknown. Here we identify protein-coding and cis-regulatory mutations in Tyrp1, Sox10, and Slc45a2 that underlie classical color phenotypes of pigeons and present a mechanistic explanation of their dominance and epistatic relationships. We also find unanticipated allelic heterogeneity at Tyrp1 and Sox10, indicating that color variants evolved repeatedly though mutations in the same genes. These results demonstrate how a spectrum of coding and regulatory mutations in a small number of genes can interact to generate substantial phenotypic diversity in a classic Darwinian model of evolution.
authors: Department of Biology, University of Utah, Salt Lake City, UT 84112, USA.
authors: Eric T
authors: ET
authors: Domyan
authors: Department of Biology, University of Utah, Salt Lake City, UT 84112, USA.
authors: Michael W
authors: MW
authors: Guernsey
authors: Department of Human Genetics, University of Utah, Salt Lake City, UT 84112, USA.
authors: Zev
authors: Z
authors: Kronenberg
authors: Department of Biology, University of Texas at Arlington, Arlington, TX 76019, USA.
authors: Shreyas
authors: S
authors: Krishnan
authors: Department of Dermatology, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USA.
authors: Raymond E
authors: RE
authors: Boissy
authors: Department of Biology, University of Utah, Salt Lake City, UT 84112, USA.
authors: Anna I
authors: AI
authors: Vickrey
authors: Department of Biology, University of Texas at Arlington, Arlington, TX 76019, USA.
authors: Clifford
authors: C
authors: Rodgers
authors: Huntsman Cancer Institute, University of Utah, Salt Lake City, UT 84112, USA; Department of Dermatology, Oregon Health & Science University, Portland, OR 97239, USA.
authors: Pamela
authors: P
authors: Cassidy
authors: Huntsman Cancer Institute, University of Utah, Salt Lake City, UT 84112, USA; Department of Dermatology, Oregon Health & Science University, Portland, OR 97239, USA.
authors: Sancy A
authors: SA
authors: Leachman
authors: Department of Biology, University of Texas at Arlington, Arlington, TX 76019, USA.
authors: John W
authors: JW
authors: Fondon
authors: Department of Human Genetics, University of Utah, Salt Lake City, UT 84112, USA.
authors: Mark
authors: M
authors: Yandell
authors: Department of Biology, University of Utah, Salt Lake City, UT 84112, USA. Electronic address: shapiro@biology.utah.edu.
authors: Michael D
authors: MD
authors: Shapiro
mesh_terms: D000818:Animals; D000951:Antigens, Neoplasm / Q000235:genetics; D030161:Avian Proteins / Q000235:genetics*; D003116:Color; D010856:Columbidae / Q000235:genetics* / Q000502:physiology; D004843:Epistasis, Genetic; D008562:Membrane Glycoproteins / Q000235:genetics; D026901:Membrane Transport Proteins / Q000235:genetics; D008969:Molecular Sequence Data; D009154:Mutation; D010088:Oxidoreductases / Q000235:genetics; D010641:Phenotype; D010858:Pigmentation; D055757:SOXE Transcription Factors / Q000235:genetics
chemical_list: D000951:Antigens, Neoplasm; D030161:Avian Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D055757:SOXE Transcription Factors; D010088:Oxidoreductases