Dog colour patterns explained by modular promoters of ancient canid origin

Meharji Arumilli ,Petra Roosje ,Gregory S Barsh ,Robert Loechel ,James R Mickelson ,Christopher B Kaelin ,Tosso Leeb ,Vidhya Jagannathan ,Katie M Minor ,Jan Henkel ,Petra Hug ,Cord Drögemüller ,Danika L Bannasch ,Anna Letko ,Hannes Lohi ,Marjo K Hytönen

doi:10.1038/s41559-021-01524-x

Abstract

Distinctive colour patterns in dogs are an integral component of canine diversity. Colour pattern differences are thought to have arisen from mutation and artificial selection during and after domestication from wolves but important gaps remain in understanding how these patterns evolved and are genetically controlled. In other mammals, variation at the ASIP gene controls both the temporal and spatial distribution of yellow and black pigments. Here, we identify independent regulatory modules for ventral and hair cycle ASIP expression, and we characterize their action and evolutionary origin. Structural variants define multiple alleles for each regulatory module and are combined in different ways to explain five distinctive dog colour patterns. Phylogenetic analysis reveals that the haplotype combination for one of these patterns is shared with Arctic white wolves and that its hair cycle-specific module probably originated from an extinct canid that diverged from grey wolves more than 2 million years ago. Natural selection for a lighter coat during the Pleistocene provided the genetic framework for widespread colour variation in dogs and wolves.

Highlights

Acentral aspect of the amazing morphologic diversity among domestic dogs is their colours and colour patterns
Specific colour patterns arise through differential regulation of Agouti (ASIP), which encodes a paracrine signalling molecule and antagonist of the melanocortin 1 receptor (MC1R) that causes hair follicle melanocytes to switch from making eumelanin to pheomelanin[1,2,3,4]
Two of the three transcripts vary in abundance between dominant yellow and black back dogs and the corresponding 5′-flanking promoters have sequence variation associated with dog pattern phenotypes

Summary

Introduction

Acentral aspect of the amazing morphologic diversity among domestic dogs is their colours and colour patterns. Specific colour patterns arise through differential regulation of Agouti (ASIP), which encodes a paracrine signalling molecule and antagonist of the melanocortin 1 receptor (MC1R) that causes hair follicle melanocytes to switch from making eumelanin (black or brown pigment) to pheomelanin (yellow to nearly white pigment)[1,2,3,4]. Asip expression is controlled by alternative promoters in specific body regions and at specific times during hair growth and gives rise to the light-bellied agouti phenotype, with ventral hair that is yellow and dorsal hair that contains a mixture of black and yellow pigment[4]. We investigate non-coding variation in ASIP regulatory modules and their effect on patterning phenotypes in domestic dogs. We expand our analysis to include modern and ancient wild canids and uncover an evolutionary history in which natural selection during the Pleistocene provided a molecular substrate for colour pattern diversity today

Methods

Results

Conclusion