Authors

G Sallé¹; S R Doyle⁴; J Cortet¹; J Cabaret¹; R Beech²; J Gilleard³; M Berriman⁴; N Holroyd⁴; J A Cotton⁴;  ¹ INRA, France;  ² Institute of Parasitology, McGill University, Canada;  ³ University of Calgary, United States;  ⁴ Wellcome Trust Sanger Institute, UK

Discussion

We have analyzed the global diversity of Haemonchus contortus populations, the most pathogenic gastro-intestinal nematode of ruminants, using low-coverage whole-genome sequencing of 265 individual males from 19 populations sampled from 13 countries. Both high nucleotide diversity (23,868,644 autosomal SNPs) and rapid decay of linkage disequilibrium with physical distance (0.09 to 0.33 at 2 Kbp) were consistent with a large effective population size (Ne) which varied between populations from 10⁵ to 15 x 10⁶ individuals. A mitochondrial sequence phylogeny of individual worms supported an out-of-Africa hypothesis, followed by radiations in Oceania and Western Europe. Close genetic relationships were observed between Caribbean and western African populations mirroring slave trade movements. A weak phylogeographic signal (Mantel’s test r=0.14, P=0.003) combined with admixture between geographically remote populations is consistent with modern sheep movement. A scan for genes under diversifying selection in African populations demonstrated enrichment for genes involved in neurogenesis and response to biotic stimuli such as heat acclimation. The region surrounding the beta-tubulin locus displayed a strong reduction in genetic diversity, presumably due to exposure to benzimidazoles. Genetic differentiation between ivermectin-resistant and –susceptible populations revealed multiple candidate regions in line with a polygenic architecture of ivermectin resistance. In contrast, comparing populations from different climatic conditions revealed two major candidate genes associated with climatic adaptation, which have orthologs associated with resistance to dessication in insects or adaptation to hot environment in C.elegans. Our results give the first global picture of genome-wide diversity in this key veterinary nematode parasite and provide valuable insights into the key factors underpinning adaptation of a parasitic nematode to a range of environmental pressures.