Dog colour patterns explained by modular promoters of ancient canid origin

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.

A novel enhancer of Agouti contributes to parallel evolution of cryptically colored beach mice

“…Moreover, this region is not highly conserved (in rodents), suggesting it may have evolved regulatory function only recently. This new regulatory element further supports the observation that Agouti regulation is highly modular (Linnen et al, 2013;Mallarino et al, 2017;Vrieling et al, 1994), which could, in turn, explain why Agouti expression may be the target of repeated evolutionary tinkering across vertebrates, for example, in rabbits (Jones et al, 2018), dogs (Bannasch et al, 2021), buffalo (Liang et al, 2021) and birds (Nadeau et al, 2008;Uy et al, 2016) -akin to other highly modular genes, such as Pax6 in vertebrates (Kammandel et al, 1999); Pitx1 in stickleback fish (Chan et al, 2010;Thompson et al, 2018); Ebony in Drosophila (Signor et al, 2016); and Asip2b/Agrp2 in cichlid fishes (Kratochwil et al, 2018). This Agouti regulatory element likely contains causal mutation(s) that affect pigmentation.…”

Canine coat pigmentation genetics: a review

“…As the Agouti locus is hypostatic to the Extension locus, the genotype at the A locus will only influence coat colour in dogs with at least one E or E m allele at MC1R. The diversity of agouti phenotypes is facilitated by the presence of alternative, independently regulated ASIP isoforms with varying temporal and spatial expression (Vrieling et al 1994;Bannasch et al 2021). Each ASIP isoform is characterised by a unique promoter and 5 0 non-coding first exon (Bannasch et al 2021).…”

“…The diversity of agouti phenotypes is facilitated by the presence of alternative, independently regulated ASIP isoforms with varying temporal and spatial expression (Vrieling et al 1994;Bannasch et al 2021). Each ASIP isoform is characterised by a unique promoter and 5 0 non-coding first exon (Bannasch et al 2021). Of these, the ventral promotor (VP) isoform of agouti is expressed exclusively on the ventral body surface and is involved in lightening of the ventral abdominal coat, whereas the hair cycle promotor (HCP) isoform is only expressed in certain stages of the hair cycle, producing hair of banded dark and light pigment across the dorsum (Vrieling et al 1994;Bannasch et al 2021).…”

“…Historically, expression of these isoforms has been attributed to diverse interactions between intronic and coding variants at this gene and a neighbouring gene, hnRNP associated with lethal yellow (RALY) (Kerns et al 2004;Berryere et al 2005;Dreger & Schmutz 2011;Ciampolini et al 2013;Dreger et al 2013). Recent research by Bannasch et al (2021) has demonstrated that ASIP expression is primarily instead controlled by independent regulatory elements located upstream of the ASIP coding sequence (Table 1). Bannasch et al (2021) mapped the ASIP VP and HCP to g.23335019 and g. 23378834 respectively (Fig.…”

“…Table 2 Phenotypic effects of the e A allele on different genetic backgrounds (Anderson et al 2020). Note that the a y , a t and a w Agouti alleles presented in this table have since been disproven as causative of A locus coat variation (Bannasch et al 2021) and are no longer used. To aid understanding, a y , a t and a w can be considered comparable with DY, BB or BS and AG respectively.…”