Although the impact of toxic exposure on our epigenome can leave a bad taste, a recent study into hydrogen sulfide transcends the senses by hitting the smell category too. Building on their previous fishy tale of transgenerational epigenetic inheritance, the lab of Michael K. Skinner (Washington State University, Pullman, WA, USA) recently explored a new species of fish (Poecilia mexicana) and how it adapts to toxic levels of foul-smelling hydrogen sulfide through the intergenerational epigenetic inheritance of specific DNA methylation patterns.
To achieve this level of insight, they formed an extreme new collaboration built on previous research that provided evidence for heritable variations in the expression in genes related to hydrogen sulfide toxicity and detoxification, which may be driven by differential microRNA expression. In their new study, the authors utilized MeDIP-seq to compare DNA methylation profiles of nucleated red blood cells from fish thriving in sulfidic and non-sulfidic natural environments and those derived from fish propagated for two generations under non-sulfidic conditions.
If something sounds rather fishy to you, let’s dive into all the interesting details of this new intergenerational epigenetic inheritance study from Kelley and colleagues to get things clear:
- A comparison of epimutations between sexes and between field and laboratory populations found significant differential DNA methylation regions (DMRs) when comparing the sulfidic and non-sulfidic populations for both the wild-caught (F0) and the laboratory-reared (F2) fish
- Both the origin and the rearing environment (wild versus laboratory) impacted DNA methylation patterns
- DMR sizes and locations in regions of low-density CpGs have similarities to environmentally responsive DMRs identified in rats
- An 80% overlap in DMRs across generations suggests intergenerational epigenetic inheritance in the absence of hydrogen sulfide
- While DMRs associate with genes involved in signaling, transcription, cytoskeleton, metabolism, and receptors, DMR-associated genes also include those related to sulfur toxicity and metabolism
- These include chondroitin sulfate–associated genes, with chondroitin sulfate being a critical component of the extracellular matrix and proteoglycans
Overall, this exciting research suggests that the DNA methylation alterations that allow this fish species to thrive in toxic conditions are inherited by subsequent generations in the absence of the environmental stressor, where they may help to support the survival of offspring in a stress-filled foul-smelling environment!
“This is not a one-off, unique species event. This has an impact on everything, including humans,” said lead author Skinner. “Although this is an animal model, it’s a demonstration of how an environmental toxicant can actually shift the epigenetics, and it becomes programmed for subsequent generations.”
For all the details on this tale of intergenerational epigenetic inheritance, see PNAS, June 2021.