Loss-of-function mutations in ASIP and MC1R are associated with coat color variation in marsupials.

Abstract

Pigment production in mammalian hair follicles is governed in part by interactions between Agouti Signalling Protein (ASIP) and the Melanocortin 1 Receptor (MC1R). The most common coat colours in mammals result from alternating bands of dark eumelanin and light pheomelanin within individual hairs. However, coats dominated by a single type of melanin have arisen several times. Here, we examine the genetic basis of two instances among the marsupials: a melanistic morph of the eastern quoll (Dasyurus viverrinus) found at high frequency in the wild, and a rare case of fixed xanthism in the marsupial moles. In the eastern quoll, we show that a deletion encompassing part of the ASIP coding sequence likely explains melanism in this species. Notably, this mutation is convergent with that recently discovered in its dark-coated relative, the Tasmanian devil (Sarcophilus harrisii). Conversely, we show that a nonsense mutation which severely truncates MC1R in the southern marsupial mole (Notoryctes typhlops) is a strong candidate driver of its pheomelanin-predominant coat. Together with other recent findings, our results suggest that loss-of-function mutations have occurred repeatedly within the marsupials, representing an important mechanism underpinning coat colour variation.