The global diversity of the major parasitic nematodeHaemonchus contortusis shaped by human intervention and climate

Abstract

The gastrointestinal parasite Haemonchus contortus is an haematophagous parasitic nematode of veterinary interest and a model for the study of drug resistance mechanisms or host-parasite interactions. To understand its evolutionary history, and its ability to adapt in the face of climatic and drug pressure, we have performed an extensive survey of genome-wide diversity using single-worm whole genome sequencing of 223 individuals sampled from 19 isolates spanning five continents. The pattern of global diversity is driven by an African origin for the species, together with contemporary dispersal that is consistent with modern human movement, with evidence for parasites spreading during the transatlantic slave trade and colonisation of Australia presented. Strong selective sweeps were identified in independent populations each surrounding the β-tubulin locus, a target of benzimidazole anthelmintic drug treatment used widely to control H. contortus infections. These signatures of selection were further supported by signals of diversifying selection enriched in genes involved in response to drugs, as well as other anthelmintic-associated biological functions including pharyngeal pumping and oviposition. From these analyses, we identify some known, and previously undescribed, candidate genes that may play a role in ivermectin resistance. Finally, we describe genetic signatures of climate-driven adaptation, revealing a gene acting as an epigenetic regulator and components of the dauer pathway may play a role in adaptation in the face of climatic fluctuations. These results begin to define genetic adaptation to climate for the first time in a parasitic nematode, and provides insight into the ongoing expansion in the range of Haemonchus contortus, which may have consequences for the management of this parasite.

Population genomic and evolutionary modelling analyses reveal a single major QTL for ivermectin drug resistance in the pathogenic nematode, Haemonchus contortus

“…As an alternative to a linear reference genome, the use of population genome graphs – a non-linear or branching reference that contains alternate paths representing known genetic variation – may be more suitable [ 51 ], and allow better characterisation of known variation that is too complex to be analysed using a linear reference [ 52 ]. This may be possible once a comprehensive analysis of population and perhaps global genetic diversity is made available [ 53 ]. Alternatively, de novo reference sequences from geographically diverse isolates may be required, ideally sequenced and assembled using long-read sequencing technology, to allow a more comprehensive description of genetic variation within a population while allowing large scale variation between reference populations to be characterised.…”

Evaluation of DNA Extraction Methods on Individual Helminth Egg and Larval Stages for Whole-Genome Sequencing

“…Continued development of genomic technologies and the associated reduction in sequencing and library preparation costs will make screening large samples by genome sequencing more routine as in viral (Dudas et al, 2017) and bacterial (Domman et al, 2018) population studies. In doing so, the ability to derive high resolution data may provide insight into, for example, (i) within host reproductive dynamics, including within host population size, differential fecundity (Hildebrandt et al, 2014), and reproductive traits such as polyandry (Doyle et al, 2018), (ii) defining parasite transmission zones and rates of transmission between zones to prioritize treatment foci (Crawford et al, 2019; this special edition, in review), (iii) defining effective population sizes of parasite populations (Sallé et al, 2019), and using this to estimate the impact of control strategies over time, and/or (iv) discrimination between reintroduction and recrudescence of parasites in regions where parasite control has been successful (Koala et al, 2019). The use of genomics to provide information-rich data will be increasingly important for diagnostic and surveillance purposes broadly (Cotton et al, 2018), and will be particularly informative as efforts to control human infective helminths using MDA move from control to elimination.…”