Year: 2020
Type: preprint
Abstract: In North American gray wolves, black coat color is dominantly inherited via a three base pair coding deletion in the canine beta defensin 3 ( CBD103 ) gene. This three base pair deletion, called the K B allele, was introduced through hybridization with dogs and subsequently underwent a selective sweep that increased its frequency in wild wolves. Despite apparent positive selection, K BB wolves have significantly lower fitness than wolves with the K yB genotype, even though the two genotypes show no observable differences in black coat color. Thus, the K B allele is thought to have pleiotropic effects on as-yet unknown phenotypes. Given the role of skin-expressed CBD103 in innate immunity, we hypothesized that the K B allele influences the gene regulatory response to viral infection. To test this hypothesis, we developed a panel of primary epidermal keratinocyte cell cultures from 24 wild North American gray wolves (both K yy and K yB genotypes) and generated immortalized K yy and CBD103 knockout lines. We assessed the transcriptome-wide responses of wolf keratinocytes to polyinosinic:polycytidylic acid (polyI:C), which mimics infection by a double-stranded RNA virus, and to live canine distemper virus. Keratinocytes with the K yB genotype and with the K yy genotype had similar gene regulatory responses to viral infection, suggesting that this response does not explain pleiotropic effects of the K B allele on fitness. This study supports the feasibility of using cell culture methods to investigate the phenotypic effects of naturally occurring genetic variation in wild mammals.
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W3113877112