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 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 [1-6], 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 [7].

A unified test of linkage analysis and rare-variant association for analysis of pedigree sequence data

“…This is especially true for species with high levels of genetic diversity such as rice 33 and maize 34 , where a large proportion of near-neutral variants may complicate the identification of mutations responsible for the phenotype. The integrated variant classification functionality in VAAST and pVAAST may mitigate these challenges 35,36 .…”

Pigeonetics takes flight: Evolution, development, and genetics of intraspecific variation

“…Whether for aesthetic or practical reasons, or a combination of the two, the genetic basis of pigmentation has been one of the most-intensively investigated fields in pigeons and other vertebrates (Domyan et al, 2014; Hubbard et al, 2010; Manceau et al, 2010; Rosenblum et al, 2014; Sulem et al, 2007). Pigeons display a tremendous amount of color variation, and rely on essentially the same pigmentation system as mammals; by varying the absolute and relative amounts of black eumelanin and red pheomelanin, a wide variety of colors can be generated (Haase et al, 1992).…”

“…The rock pigeon now has a high-quality reference genome, additional re-sequenced genomes representing a wide variety of breeds (NCBI Bioproject PRJNA284526), a catalog of over 25 million SNPs and genomic structural variants across breeds, and a draft genome-wide linkage map (Domyan et al, 2014; Domyan et al, 2016; Shapiro et al, 2013). These extensive resources, combined with standard experimental techniques developed for canonical model systems, make the pigeon a viable model to understand the genetic basis of phenotypic variation, and to test the developmental consequences of these genetic variants in developing embryos.…”

“…Furthermore, relatively complex traits (feather color, for instance) can sometimes be genetically teased apart into discrete components (e.g., by treating the type and intensity of melanin as separate traits), thereby facilitating mapping of each component (Domyan et al, 2014). …”

Diversidad Genética de Palomas Domésticas (Columba livia) en Lorica, Colombia, Utilizando Genes que Codifican la Coloración del Plumaje

“…Estudios de mecanismos selectivos que permiten el mantenimiento de polimorfismo en poblaciones naturales de palomas domés-ticas han demostrado cómo un espectro de codificación y mutaciones reguladoras en un pequeño número de genes puede interactuar para generar diversidad fenotípica sustancial en un modelo clásico de evolución darwiniana (Domyan et al, 2014).…”