3.6 | Potential drivers of divergence
Currently, the anthelmintics mainly have two modes of action, one is
more rapid action on membrane ion channels, and the other is a
relatively slow biochemical reaction. These common anthelmintics include
benzimidazoles (BZs), macrolides (MLs), nicotinic acetylcholine receptor
agonists (Wolf et al.) and aminoacetonitrile derivatives (AADs). We
screened out the main genes that may be related to the resistance of all
the above-mentioned anthelmintics that have been reported so far (Table
1). We performed selective scanning (iHS) within 50 kb of all these gene
regions, and calculated the nucleotide diversity (π ) andtajima’D of the three populations with 10 kb sliding windows. The
results showed that multiple resistance-related genes were strongly
selected among different populations (positive or negative; Table 1).
For example, we first identified three classic resistance locus
(167/Phe, 198/Glu and 200/Phe) of the BZs resistance gene β-tubulin
(Lake, Matthews, Kaplan, & Hodgkinson, 2009), and found that all
individuals in the three populations showed non-resistant mutations
through sequence alignment (Fig. S14a). We then further scanned the
selection of these gene regions and found that although there were no
drug-resistant mutations in these regions, and they showed significant
positive selection (Fig. S14c). In addition, the selection of other
resistance-related genes in the population have also been discovered
(Fig. S15 - S17). For example, multidrug resistance protein pgp-3and multidrug resistance protein 1 (mrp-1 ) revealed strong
positive selections in the PEc population. Glutamate-gated chloride
channel alpha (glc-1 ), which was related to ivermectin
resistance, showed strong positive selection in PEz and PEa populations.
The selection of these regions do not have a certain rule, which may be
related to the medication history in different environments. However, it
was obvious that in some groups, certain genetic selections have been
permanent and would continue to be passed down to the next generation.
4 | DISCUSSION
The ecological environment in which parasites inhabit is different from
that of ordinary animals, and the survival of parasites is more
dependent on the intestinal environment. The survival and evolution of
the equine are inextricably linked to nature and human activities. Our
study used a combination of explicit genetic analysis and demographic
models to determine the possibly diversified mechanisms that occur in
different intestinal environments. We applied δaδi 2D/3D models to
roundworm populations distributed in different regions and different
hosts to unveil whether the diversity of the population was caused by
geographic distribution and ecological environment, or simply caused by
host specificity, or was related to human domestication of its host. The
ancient migration or secondary contact model, as well as the immediate
size change model, were found to be effective in explaining the
demographic differences and recent divergence of Parascaris spp.
populations. In addition, the demographic history showed that theParascaris spp. were in the process of divergence. Selection
analysis provided evidence for understanding the possible causes of the
divergence, which supports the significant impact of different
intestinal habitats on evolution. We summarized the main findings on the
diversification of Equus roundworms, and provided a perspective
for future monitoring of roundworm ecology in a timely manner to deal
with possible unfavorable mutations.