1 and 2c), which indicates that the VP and HCP haplotypes function separately from each other. Importantly, increased activity from the ventral promoter (VP1 versus VP2) correlates with dorsal expansion of yellow pigment in black saddle compared to black back phenotypes (Figs. 2b) and fails to complement HCP3 or HCP5 (Fig. Because the level of ASIP activity is directly related to the amount of yellow pigment production, these genetic association results suggest that VP1 has greater activity than VP2, HCP1 has greater activity than HCP2 and HCP3, 4 and 5 all represent loss-of-function, since the HCP4 haplotype includes a large deletion of the hair cycle first exon (Fig. Black saddle and black back dogs differ in their VP configuration but all carry HCP3, 4 and/or 5 in homozygous or compound heterozygous configurations. For example, homozygotes for VP1-HCP1, VP2-HCP1, VP2-HCP2 are dominant yellow, shaded yellow and agouti, respectively (Supplementary Tables 4– 7). 2c and Table 1, diplotype combinations of VP1 or VP2 with HCP1, 2, 3, 4 or 5 are correlated perfectly with variation in ASIP pattern phenotype. These results were extended by developing PCR-based genotyping assays for the VP and HCP structural variants, examining their association with different pattern phenotypes in 352 dogs from 34 breeds and comparing these results to previously published variants (Table 1, Extended Data Fig. All structural variants were precisely delineated with Sanger sequencing. 2b left and Supplementary Table 1) the five HCP haplotypes differ according to the number and identity of SINE elements, all in the same orientation as ASIP, as well as additional insertions and deletions (Fig. VP1 contains a SINE element in reverse orientation relative to the transcription of ASIP and an A-rich expansion not found in VP2 (Fig. We used dogs that were homozygous at the ASIP locus to infer two VP haplotypes and five HCP haplotypes, consisting of multiple structural variants that lie within 1.5 kb of each transcriptional start site. To better understand the relationship between promoter usage and pattern phenotypes, we inspected whole genome sequence data from 77 dog and wolf samples with known colour patterns (Supplementary Table 3). 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. Here we investigate non-coding variation in ASIP regulatory modules and their effect on patterning phenotypes in domestic dogs. Genetic variation in ASIP affects colour pattern in many mammals however, in dogs, the situation is still unresolved, in large part due to the complexity of different pattern types, epistatic relationships with variants at other loci and challenges in distinguishing whether genetic association of one or more variants truly represents causal variation or just close linkage 5. In laboratory mice, 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. ![]() In many mammals, 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. Natural selection for a lighter coat during the Pleistocene provided the genetic framework for widespread colour variation in dogs and wolves.Ī central aspect of the amazing morphologic diversity among domestic dogs is their colours and 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. Structural variants define multiple alleles for each regulatory module and are combined in different ways to explain five distinctive dog colour patterns. Here, we identify independent regulatory modules for ventral and hair cycle ASIP expression, and we characterize their action and evolutionary origin. In other mammals, variation at the ASIP gene controls both the temporal and spatial distribution of yellow and black pigments. ![]() 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. Distinctive colour patterns in dogs are an integral component of canine diversity.
0 Comments
Leave a Reply. |
AuthorWrite something about yourself. No need to be fancy, just an overview. ArchivesCategories |