The methylome of Biomphalaria glabrata and other mollusks: enduring modification of epigenetic landscape and phenotypic traits by a new DNA methylation inhibitor
Abstract:5-methylcytosine (5mC) is an important epigenetic mark in eukaryotes. Little information about its role exists for invertebrates. How 5mC contributes to phenotypic variation in invertebrates can be investigated by experimental alteration of methylation patterns. Here, we apply new non-nucleoside DNA methyltransferase inhibitors (DNMTi) to introduce global changes into the methylome of mollusk species. Flavanone inhibitor Flv1 was highly efficient in reducing 5mC in the freshwater snails Biomphalaria glabrata a… Show more
“…Furthermore, we previously demonstrated that DNA methyltransferase (DNMT) inhibitors induce phenotypic diversity in the morphometric traits of treated B. glabrata snails and its offspring (Luviano et al, 2021). We also showed that DNA methylation is essential for the snail (Luviano et al, 2023). Both, the existing knowledge on DNA methylation and phenotypic responsiveness to infestation make B. glabrata snails are an ideal system to study the role of DNA methylation in the generation of phenotypic plasticity.…”
DNA methylation variation may play a role in phenotypic variation as it can be directly affected by the environment and be inherited. DNA methylation variations were introduced into the parasite vector snail Biomphalaria glabrata with low genetic diversity by chemical treatment in F0 and followed over 3 generations using epigenetic recombinant inbred lines (epiRILs). We observed phenotypic variation in complex traits such as fecundity and susceptibility to infestation by Schistosoma mansoni and DNA methylation differences in F3. Both, increase and decrease of infestation success (up to 100% and down to 20% prevalence in epiRILs and from 86% to 94% in control RILs) indicated variation in complex resistance/compatibility trait. Average prevalence in control RILs was 84+/-5% but only 68+/-21 % in epiRILs. Fecundity also changed and was in average 47+/-7% in control RILs and 59+/-18% in epiRILs, being 12% higher in epiRILs. We found that the heritability h2 of the fecundity in the epiRILs was between 0.5 and 0.6 depending on the method used to estimate it. We developed a model for introducing epimutant offspring snails into resident susceptible populations. If genetic assimilation of the resistant phenotype occured in a small fraction of the introduced epimutant snails, we predict that the susceptible phenotype is replaced by the resistant phenotype after 50-70 generations.
“…Furthermore, we previously demonstrated that DNA methyltransferase (DNMT) inhibitors induce phenotypic diversity in the morphometric traits of treated B. glabrata snails and its offspring (Luviano et al, 2021). We also showed that DNA methylation is essential for the snail (Luviano et al, 2023). Both, the existing knowledge on DNA methylation and phenotypic responsiveness to infestation make B. glabrata snails are an ideal system to study the role of DNA methylation in the generation of phenotypic plasticity.…”
DNA methylation variation may play a role in phenotypic variation as it can be directly affected by the environment and be inherited. DNA methylation variations were introduced into the parasite vector snail Biomphalaria glabrata with low genetic diversity by chemical treatment in F0 and followed over 3 generations using epigenetic recombinant inbred lines (epiRILs). We observed phenotypic variation in complex traits such as fecundity and susceptibility to infestation by Schistosoma mansoni and DNA methylation differences in F3. Both, increase and decrease of infestation success (up to 100% and down to 20% prevalence in epiRILs and from 86% to 94% in control RILs) indicated variation in complex resistance/compatibility trait. Average prevalence in control RILs was 84+/-5% but only 68+/-21 % in epiRILs. Fecundity also changed and was in average 47+/-7% in control RILs and 59+/-18% in epiRILs, being 12% higher in epiRILs. We found that the heritability h2 of the fecundity in the epiRILs was between 0.5 and 0.6 depending on the method used to estimate it. We developed a model for introducing epimutant offspring snails into resident susceptible populations. If genetic assimilation of the resistant phenotype occured in a small fraction of the introduced epimutant snails, we predict that the susceptible phenotype is replaced by the resistant phenotype after 50-70 generations.
“…The pipeline is available at: . The filtered and demultiplexed reads from epiGBS2 pipeline were used in another pipeline adapted from previous work [ 33 ], using the Galaxy project server as applied in [ 34 ]. Adapter removing was done using TrimGalore!…”
The phenotypic plasticity of plants in response to change in their light environment, and in particularly, to shade is a schoolbook example of ecologically relevant phenotypic plasticity with evolutionary adaptive implications. Epigenetic variation is known to potentially underlie plant phenotypic plasticity. Yet, little is known about its role in ecologically and evolutionary relevant mechanisms shaping the diversity of plant populations in nature. Here we used a reference-free reduced representation bisulfite sequencing method for non-model organisms (epiGBS) to investigate changes in DNA methylation patterns across the genome in snapdragon plants (Antirrhinum majus L.). We exposed plants to sunlight versus artificially induced shade in four highly inbred lines to exclude genetic confounding effects. Our results showed that phenotypic plasticity in response to light versus shade shaped vegetative traits. They also showed that DNA methylation patterns were modified under light versus shade, with a trend towards global effects over the genome but with large effects found on a restricted portion. We also detected the existence of a correlation between phenotypic and epigenetic variation that neither supported nor rejected its potential role in plasticity. While our findings imply epigenetic changes in response to light versus shade environments in snapdragon plants, whether these changes are directly involved in the phenotypic plastic response of plants remains to be investigated. Our approach contributed to this new finding but illustrates the limits in terms of sample size and statistical power of population epigenetic approaches in non-model organisms. Pushing this boundary will be necessary before the relationship between environmentally induced epigenetic changes and phenotypic plasticity is clarified for ecologically relevant mechanisms with evolutionary implications.
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