Experimental Parasite Infection Causes Genome-Wide Changes in DNA Methylation

Mol Biol Evol. 2020 Aug 1;37(8):2287-2299. doi: 10.1093/molbev/msaa084.

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.

Keywords: DNA methylation; epigenetics; host–parasite interactions; reduced representation bisulfite sequencing; three-spined stickleback.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Camallanina / physiology*
  • DNA Methylation*
  • Genetic Fitness
  • Genome
  • Host-Pathogen Interactions*
  • Male
  • Parasite Load*
  • Phenotype
  • Smegmamorpha / genetics
  • Smegmamorpha / parasitology*