Scientists study how selective mating in nematodes can lead to permanent epigenetic changes

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If the study of epigenetics has taught us anything, it’s that we can no longer blame all of our biological heritage solely on our DNA. Some of this blame can be attributed to the environment our parents or grandparents were exposed to during their lifetimes. The alterations in their epigenetic profile resulting from these exposures can be transmitted to the offspring.

Researchers call this phenomenon epigenetic inheritance, and it explains how certain stimuli such as diet, toxins, and even trauma experienced in a generation can affect the physical and mental health of future generations.

The accumulation of evidence gathered over the decades supports the notion of epigenetic inheritance. However, the process by which it occurs is not fully known. Researchers haven’t had a simple way to analyze it, especially with regard to the persistent epigenetic changes that affect an entire lineage.

Scientists at the University of Maryland (UMD) set out to tackle this mystery and found a way to study inherited epigenetic changes using a simple approach. In their research published in Nature Communication, they used selective mating as a tactic to create permanent epigenetic changes that have been maintained in over 300 generations of nematode worms.

Epigenetic mutations, unlike genetic mutations, do not alter the sequence of the genome and are potentially reversible. When an organism reproduces, these types of changes can be inherited or repaired and will often dissipate in subsequent offspring. It is rare to find stable epigenetic changes that last for hundreds of generations. But they have been seen in a variety of systems and are usually maintained by mechanisms, such as DNA methylation, that involve positive feedback to duplicate or amplify the mutation.

In several articles, we have discussed how DNA methylation and histone changes can be passed from parent to child. We also reviewed the role epigenetics play in domestication, which is a type of evolutionary change that occurs when acquired epigenetic marks are inherited over several generations.

The study originated when the research team first discovered that the nematode worms they were breeding continued to pass on the same epigenetic mutation with each additional generation, regardless of how many times they reproduced them. The species they used, C. elegans, is a biological model organism often used in research. They can be dioecious, with separate male and female individuals, and are easily handled for breeding experiments.

Here, the researchers noticed that the worms bred to carry a gene to produce fluorescent proteins occasionally glowed but had virtually the same DNA. This anomaly led them to conduct more experiments to better understand what was going on. While only one parent must carry the gene for the offspring to shine, the offspring always shone when the mother had it, but when the gene came from the father, it rarely shines or not at all.

“We found that these RNA-based signals control gene expression“said Antony Jose, lead author of the study and associate professor of cell biology and molecular genetics at UMD.” Some of these signals silence the gene and some of them are protective signals that prevent the silence. These signals clash as the offspring develop. When the gene comes from the mother, the protective signal always wins, but when the gene comes from the father, the silence signal almost wins always.

Once silence is initiated through male inheritance, it remains so forever or at least considering that it has been tested in this way over 300 generations. Epigenetic changes are complex and it is rare to find any that can last more than a few lifecycles, making them difficult to study. Thus, the use of a tool like mating-induced RNA silencing opens the door to exploring the details of epigenetic inheritance like never before.

Yet not all genes can be studied this way, as most will usually recover from the silence and speak out in future generations. At the same time, it has now become clear that certain genes are vulnerable to permanent epigenetic changes.

The main lessons from this study are that mating can be used to easily induce long-lasting epigenetic changes, and the onset of this phenomenon occurs at the level of a single gene.

As Jose said, “Now we can manipulate this gene and control everything about it, which will allow us to determine what characteristics make a gene susceptible or resistant to hereditary epigenetic change. “

While more research is needed to identify other genes vulnerable to long-lasting epigenetic changes, the team hopes future scientists will have a better understanding of epigenetic inheritance and the biological processes involved, not just in animal models. but also in humans.

Source: S. Devanapally et al. (2021). Mating can initiate a stable RNA silencer that overcomes epigenetic recovery. Nature Communication.

Reference: Match matters: The right combination of parents can turn off a gene indefinitely University of Maryland, College of Computer Science, Mathematics, and Natural Sciences. July 9, 2021.


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