Research Report 2019_20


Modular promoter expression explains Agouti patterns

dominant yellow ASIP allele looks almost the same as the ASIP allele of Arctic grey wolves. Construction of a phylogenetic tree showed that the dominant yellow allele was likely introduced after the grey wolf and arctic grey wolf families split on the tree. Interestingly, they did not find the ASIP hair cycle promoter that controls dominant yellow color in any other living dog. The team concluded that the promot- er was from a ghost lineage, meaning it came from an extinct dog species. Thus, arctic wolves and domestic dogs preserve the genetic legacy of an ice age canid in their pale coats, through natural and artificial selection. The work on cat color patterns was carried out by HudsonAlpha senior scientists Chris Kaelin, PhD and Kelly McGowan, PhD; the work on dog and wolf an- cestry was carried out by Chris Kaelin, PhD in collab- oration with the research groups of Tosso Leeb, PhD (University of Bern) and Danika Bannasch, PhD, DVM (UC Davis). Taken together, this work provides new in- sight into biologic building blocks that give rise to period- ic body structures such as digits and vertebrae (as well as stripes and spots), and helps us understand the origin and evolution of the natural world in which we live. n

In mammals, specific color patterns arise through differential regulation of a gene called Agouti ( ASIP ) which encodes a signaling molecule that causes hair follicle melanocytes to switch from making eumelanin (black or brown) to pheomelanin (yellow to nearly white). Through analysis of skin RNA-seq data from dogs with different coat patterns, Barsh and his colleagues deter- mined that variants in two promoters of ASIP , ventral promoter (VP) and hair color promoter (HCP), control coat color in different parts of the dog’s body. Genetic variation in the promoters explains five dis- tinctive dog color patterns—dominant yellow, shaded yellow, agouti, black saddle, and black back. For exam- ple, dogs with black back coloration have solid black bodies but yellow paws and faces. Lack of expression of any one of several variants of hair cycle promoter turns off ASIP expression in the body of the dogs, while ex- pression of ventral promoters turns on ASIP expression in the paws and face. Barsh’s lab expanded this analysis to include modern and ancient wild dogs and uncovered the evolutionary history of the promoter. Through ge- nome sequence analysis, they determined that the

2019-20 Research Report 9

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