Abstract
Parasites are arguably among the strongest drivers of natural selection, constraining hosts to evolve resistance and tolerance mechanisms. Although, the genetic basis of adaptation to parasite infection has been widely studied, little is known about how epigenetic changes contribute to parasite resistance and eventually, adaptation. Here, we investigated the role of host DNA methylation modifications to respond to parasite infections. In a controlled infection experiment, we used the three-spined stickleback fish, a model species for host–parasite studies, and their nematode parasite Camallanus lacustris. We showed that the levels of DNA methylation are higher in infected fish. Results furthermore suggest correlations between DNA methylation and shifts in key fitness and immune traits between infected and control fish, including respiratory burst and functional trans-generational traits such as the concentration of motile sperm. We revealed that genes associated with metabolic, developmental, and regulatory processes (cell death and apoptosis) were differentially methylated between infected and control fish. Interestingly, genes such as the neuropeptide FF receptor 2 and the integrin alpha 1 as well as molecular pathways including the Th1 and Th2 cell differentiation were hypermethylated in infected fish, suggesting parasite-mediated repression mechanisms of immune responses. Altogether, we demonstrate that parasite infection contributes to genome-wide DNA methylation modifications. Our study brings novel insights into the evolution of vertebrate immunity and suggests that epigenetic mechanisms are complementary to genetic responses against parasite-mediated selection.
Highlights
Evolutionary theory predicts that the adaptive potential of a population primarily relies on its genomic variation (Frankham et al 2002)
In a recent split-clutch design experiment, Kaufmann et al (2014) demonstrated transgenerational effects of parasite resistance to the nematode Camallanus lacustris, a common parasite, with clear fitness benefits for the offspring, but the underlying mechanisms awaited investigation. Based on this previous study, using reduced representation bisulfite sequencing (RRBS) (Meissner et al 2005), we focused on the methylation of cytosine-phosphate-guanine (CpG) dinucleotides (CpG sites), the most common methylation motif in vertebrates
We found that infected fish were less heavy than uninfected ones (767.29 6 294.62 mg vs. 848.11 6 228.43 mg; F1,44 1⁄4 5.41, P 1⁄4 0.024), the mean fish length showed no significant differences (40.25 6 4.47 mm vs. 41.15 6 3.58 mm; F1,44 1⁄4 2.52, P 1⁄4 0.119)
Summary
Evolutionary theory predicts that the adaptive potential of a population primarily relies on its genomic variation (Frankham et al 2002). Resolving the molecular basis of phenotypic plasticity could be the missing piece of the puzzle for a better understanding of the adaptive potential of populations or species (Eizaguirre and Baltazar-Soares 2014; Rey et al 2020). Epigenetic mechanisms are important environmentmodulated mechanisms possibly accelerating adaptive responses to selection (Gugger et al 2016; Artemov et al 2017; Metzger and Schulte 2017).
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