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K Locus Effects in Gray Wolves: Experimental Assessment of TLR3 Signaling and the Gene Expression Response to Canine Distemper Virus.

Publication ,  Journal Article
Johnston, RA; Rheinwald, JG; vonHoldt, BM; Stahler, DR; Lowry, W; Tung, J; Wayne, RK
Published in: The Journal of heredity
August 2021

In North American gray wolves, black coat color is dominantly inherited via a 3 base pair coding deletion in the canine beta defensin 3 (CBD103) gene. This 3 base pair deletion, called the KB allele, was introduced through hybridization with dogs and subsequently underwent a selective sweep that increased its frequency in wild wolves. Despite apparent positive selection, KBB wolves have lower fitness than wolves with the KyB genotype, even though the 2 genotypes show no observable differences in black coat color. Thus, the KB 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 KB allele influences the keratinocyte gene expression response to TLR3 pathway stimulation and/or infection by canine distemper virus (CDV). To test this hypothesis, we developed a panel of primary epidermal keratinocyte cell cultures from 24 wild North American gray wolves of both Kyy and KyB genotypes. In addition, we generated an immortalized Kyy line and used CRISPR/Cas9 editing to produce a KyB line on the same genetic background. We assessed the transcriptome-wide responses of wolf keratinocytes to the TLR3 agonist polyinosinic:polycytidylic acid (polyI:C), and to live CDV. K locus genotype did not predict the transcriptional response to either challenge, suggesting that variation in the gene expression response does not explain pleiotropic effects of the KB 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.

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Published In

The Journal of heredity

DOI

EISSN

1465-7333

ISSN

0022-1503

Publication Date

August 2021

Volume

112

Issue

5

Start / End Page

458 / 468

Related Subject Headings

  • Wolves
  • Toll-Like Receptor 3
  • Gene Expression
  • Evolutionary Biology
  • Dogs
  • Distemper Virus, Canine
  • Animals
  • Alleles
  • 3105 Genetics
  • 3104 Evolutionary biology
 

Citation

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Johnston, R. A., Rheinwald, J. G., vonHoldt, B. M., Stahler, D. R., Lowry, W., Tung, J., & Wayne, R. K. (2021). K Locus Effects in Gray Wolves: Experimental Assessment of TLR3 Signaling and the Gene Expression Response to Canine Distemper Virus. The Journal of Heredity, 112(5), 458–468. https://doi.org/10.1093/jhered/esab029
Johnston, Rachel A., James G. Rheinwald, Bridgett M. vonHoldt, Daniel R. Stahler, William Lowry, Jenny Tung, and Robert K. Wayne. “K Locus Effects in Gray Wolves: Experimental Assessment of TLR3 Signaling and the Gene Expression Response to Canine Distemper Virus.The Journal of Heredity 112, no. 5 (August 2021): 458–68. https://doi.org/10.1093/jhered/esab029.
Johnston RA, Rheinwald JG, vonHoldt BM, Stahler DR, Lowry W, Tung J, et al. K Locus Effects in Gray Wolves: Experimental Assessment of TLR3 Signaling and the Gene Expression Response to Canine Distemper Virus. The Journal of heredity. 2021 Aug;112(5):458–68.
Johnston, Rachel A., et al. “K Locus Effects in Gray Wolves: Experimental Assessment of TLR3 Signaling and the Gene Expression Response to Canine Distemper Virus.The Journal of Heredity, vol. 112, no. 5, Aug. 2021, pp. 458–68. Epmc, doi:10.1093/jhered/esab029.
Johnston RA, Rheinwald JG, vonHoldt BM, Stahler DR, Lowry W, Tung J, Wayne RK. K Locus Effects in Gray Wolves: Experimental Assessment of TLR3 Signaling and the Gene Expression Response to Canine Distemper Virus. The Journal of heredity. 2021 Aug;112(5):458–468.
Journal cover image

Published In

The Journal of heredity

DOI

EISSN

1465-7333

ISSN

0022-1503

Publication Date

August 2021

Volume

112

Issue

5

Start / End Page

458 / 468

Related Subject Headings

  • Wolves
  • Toll-Like Receptor 3
  • Gene Expression
  • Evolutionary Biology
  • Dogs
  • Distemper Virus, Canine
  • Animals
  • Alleles
  • 3105 Genetics
  • 3104 Evolutionary biology