PT  - JOURNAL ARTICLE
AU  - Shreyas Krishnan
AU  - Richard L. Cryberg
TI  - Effects of mutations in pigeon <em>Mc1r</em> implicate an expanded plumage color patterning regulatory network
AID  - 10.1101/792945
DP  - 2019 Jan 01
TA  - bioRxiv
PG  - 792945
4099  - http://biorxiv.org/content/early/2019/10/09/792945.short
4100  - http://biorxiv.org/content/early/2019/10/09/792945.full
AB  - Studies in mammals have shown that the Melanocortin 1 receptor occupies a pivotal role as a nexus for integrating paracrine and autocrine signals to regulate pigment production and type-switching between pheomelanin (red/yellow) and eumelanin (black/brown) pigment synthesis in melanocytes. Inactivating mutations in the Mc1r gene are responsible for recessive pheomelanic reddening traits in several species, while mutations that increase activity cause dominant eumelanic darkening traits in mammals and birds. Previous efforts to associate Mc1r coding variants with color variation in pigeons (Columba livia) have yielded conflicting results. Applying a reverse genomic approach, we discovered a novel 500 base pair frameshifting deletion in pigeon Mc1r that likely inactivates the single-exon gene. Segregation analysis revealed complete cosegregation (LOD = 12.2) with smoky (symbol sy), a recessive pigmentation trait reported in these pages by Willard F. Hollander 80 years ago. We coupled these findings with breeding tests to determine that Dirty (V), a dominant darkening trait, is allelic to sy, and identified two independent V alleles, one of which is associated with melanic morphs of two other bird species. In contrast to observations that Mc1r inactivation results in uniform pheomelanic pelage in mammals, its loss in otherwise wild-type pigeons occurs without apparent pheomelanism, instead increasing plumage eumelanism while leaving black bar pattern elements of the tail and wing largely intact. These findings require reconsideration of Mc1r’s presumed role in pigment type-switching in birds, and suggest the existence of Mc1r-independent pathways for eumelanic pigmentation pattern regulation unknown in mammals.