Over-expression and increased copy numbers of a cytochrome P450 and two UDP-glucuronosyltransferase genes in macrocyclic lactone resistant Psoroptes ovis of cattle

Abstract

Psoroptes ovis is a mite species that feeds on sheep, cattle, other ungulates, rabbits, and horses, which can develop into a severe exudative dermatitis known as psoroptic mange. The macrocyclic lactone (ML) family of acaricides are commonly used to control psoroptic mange. However, certain strains of cattle and sheep mites have developed resistance against MLs, which has led to reduced treatment efficacy and even treatment failure. Here we investigated the genetic basis of ML resistance in P. ovis mites collected from cattle across Belgium. We compared gene expression between susceptible and resistant mites before and after exposure to ivermectin and genetic diversity between a single susceptible and resistant populations. We generated chromosomal genome assemblies of P. ovis derived from sheep and cattle respectively and correlated genomic diversity of susceptible and resistant P. ovis populations sampled across Belgium. Gene expression data revealed constitutive over-expression of a cytochrome P450 monooxygenase (CYP) gene and two tandemly located UDP-glucuronosyltransferase (UGT) genes among others. On investigation of the genomic data, we observed copy number variation at both loci in population genomic data. The CYP gene is not amplified in the susceptible population but occurs in multiple copies in all resistant populations and is associated with a peak in Fst between resistant and susceptible populations indicative of selection. By contrast, the two UGT genes are massively and tandemly amplified in all populations including the susceptible dataset with weaker Fst between populations than the amplified CYP gene. Hence, distinct mechanisms of amplification and gene regulation are occurring at these putative resistance loci in P. ovis.