A copy number variant is associated with a spectrum of pigmentation patterns in the rock pigeon ( Columba livia )

ABSTRACT Rock pigeons (Columba livia) display an extraordinary array of pigment pattern variation. One such pattern, Almond, is characterized by a variegated patchwork of plumage colors that are distributed in an apparently random manner. Almond is a sex-linked, semi-dominant trait controlled by the classical Stipper (St) locus. Heterozygous males (ZStZ+ sex chromosomes) and hemizygous Almond females (ZStW) are favored by breeders for their attractive plumage. In contrast, homozygous Almond males (ZStZSt) develop severe eye defects and lack all plumage pigmentation, suggesting that higher dosage of the mutant allele is deleterious. To determine the molecular basis of Almond, we compared the genomes of Almond pigeons to non-Almond pigeons and identified a candidate St locus on the Z chromosome. We found a copy number variant (CNV) within the differentiated region that captures complete or partial coding sequences of four genes, including the melanosome maturation gene Mlana. We did not find fixed coding changes in genes within the CNV, but all genes are misexpressed in regenerating feather bud collar cells of Almond birds. Notably, six other alleles at the St locus are associated with depigmentation phenotypes, and all exhibit expansion of the same CNV. Structural variation at St is linked to diversity in plumage pigmentation and gene expression, and thus provides a potential mode of rapid phenotypic evolution in pigeons. AUTHOR SUMMARYThe genetic changes responsible for different animal color patterns are poorly understood, due in part to a paucity of research organisms that are both genetically tractable and phenotypically diverse. Domestic pigeons (Columba livia) have been artificially selected for many traits, including an enormous variety of color patterns that are variable both within and among different breeds of this single species. We investigated the genetic basis of a sex-linked color pattern in pigeons called Almond that is characterized by a sprinkled pattern of plumage pigmentation. Pigeons with one copy of the Almond allele have desirable color pattern; however, male pigeons with two copies of the Almond mutation have severely depleted pigmentation and congenital eye defects. By comparing the genomes of Almond and non-Almond pigeons, we discovered that Almond pigeons have extra copies of a chromosome region that contains a gene that is critical for the formation of pigment granules. We also found that different numbers of copies of this region are associated with varying degrees of pigment reduction. The Almond phenotype in pigeons bears a remarkable resemblance to Merle coat color mutants in dogs, and our new results from pigeons suggest that similar genetic mechanisms underlie these traits in both species. Our work highlights the role of gene copy number variation as a potential driver of rapid phenotypic evolution.