AbstractThe parasitic nematode Haemonchus contortus is an economically and clinically important pathogen of small ruminants, and a model system for understanding the mechanisms and evolution of traits such as anthelmintic resistance. Anthelmintic resistance is widespread and is a major threat to the sustainability of livestock agriculture globally; however, little is known about the genome architecture and parameters such as recombination that will ultimately influence the rate at which resistance may evolve and spread. Here we performed a genetic cross between two divergent strains of H. contortus, and subsequently used whole-genome re-sequencing of a female worm and her brood to identify the distribution of genome-wide variation that characterises these strains. Using a novel bioinformatic approach to identify variants that segregate as expected in a pseudo-testcross, we characterised linkage groups and estimated genetic distances between markers to generate a chromosome-scale F1 genetic map composed of 1,618 SNPs. We exploited this map to reveal the recombination landscape, the first for any parasitic helminth species, demonstrating extensive variation in recombination rate within and between chromosomes. Analyses of these data also revealed the extent of polyandry, whereby at least eight males were found to have contributed to the genetic variation of the progeny analysed. Triploid offspring were also identified, which we hypothesise are the result of nondisjunction during female meiosis or polyspermy. These results expand our knowledge of the genetics of parasitic helminths and the unusual life-history of H. contortus, and will enable more precise characterisation of the evolution and inheritance of genetic traits such as anthelmintic resistance. This study also demonstrates the feasibility of whole-genome resequencing data to directly construct a genetic map in a single generation cross from a non-inbred non-model organism with a complex lifecycle.Author summaryRecombination is a key genetic process, responsible for the generation of novel genotypes and subsequent phenotypic variation as a result of crossing over between homologous chromosomes. Populations of strongylid nematodes, such as the gastrointestinal parasites that infect livestock and humans, are genetically very diverse, but little is known about patterns of recombination across the genome and how this may contribute to the genetics and evolution of these pathogens. In this study, we performed a genetic cross to quantify recombination in the barber’s pole worm, Haemonchus contortus, an important parasite of sheep and goats. The reproductive traits of this worm make standard genetic crosses challenging, but by generating whole-genome sequence data from a female worm and her offspring, we identified genetic variants that act as though they come from a single mating cross, allowing the use of standard statistical approaches to build a genetic map and explore the distribution and rates of recombination throughout the genome. A number of genetic signatures associated with H. contortus life history traits were revealed in this analysis: we extend our understanding of multiple paternity (polyandry) in this species, and provide evidence and explanation for sporadic increases in chromosome complements (polyploidy) among the progeny. The resulting genetic map will aid in population genomic studies in general and enhance ongoing efforts to understand the genetic basis of resistance to the drugs used to control these worms, as well as for related species that infect humans throughout the world.
Genomic landscape of drug response reveals novel mediators of anthelmintic resistance
