If the study of epigenetics has
taught us anything, it’s that we can no longer blame our entire biological
inheritance solely on our DNA. Part of that blame can be traced back to the
environment that our parents or grandparents were exposed to during their
lifetime. Alterations in their epigenetic profile that resulted from these
exposures have the potential to be passed on to descendants.
Researchers call this phenomenon epigenetic heredity, and it explains how certain stimuli such as diet, toxins, and even trauma experienced in one generation can affect the physical and mental health of future generations.
Accumulating evidence collected over decades supports the notion
of epigenetic heredity. However, the process by which it occurs is not entirely
known. Researchers haven’t had an easy way to analyze it, especially concerning
persistent epigenetic changes that affect an entire lineage.
Scientists at the University of Maryland (UMD) decided to tackle
this mystery and have come up with a way to study inherited epigenetic
modifications using a simple approach. In their research published in Nature Communications, they used
selective mating as a tactic to create permanent epigenetic changes that were
maintained in over 300 generations of nematode worms.
Epigenetics mutations, unlike genetic ones, do not alter the
genome sequence and are potentially reversible. When an organism reproduces,
these types of modifications can be inherited or repaired and will often
dissipate in subsequent offspring. Finding stable epigenetic changes that last
for hundreds of generations is rare. But they have been observed in various
systems and are usually maintained by mechanisms, such as DNA
methylation, that involve positive feedback for duplicating or amplifying
In several articles, we have discussed how DNA methylation
modifications can be transmitted from parent to child. We have also
reviewed the role epigenetics plays in domestication, which is a type of
evolutionary change that takes place 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 kept passing on the same epigenetic
mutation to each additional generation – no matter how many times they bred
them. The species they were using, C. elegans, is a biological
model organism often used in research. They can be dioecious, with separate
male and female individuals, and are easily manipulated for reproductive
Here, the researchers noticed that the worms bred to carry a gene for producing fluorescent proteins glowed occasionally yet had virtually the same DNA. This anomaly led them to conduct more experiments to understand better what was going on. While only one parent needs to carry the gene for the offspring to glow, the offspring always glowed when the mother had it, yet when the gene came from the father, it rarely glowed or didn’t at all.
“We found that there are these RNA-based signals
controlling gene expression,” said Antony Jose, senior 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 silencing. These signals are duking it out
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 silencing
signal almost always wins.”
Once the silencing is initiated via the male inheritance, it
remains that way forever or at least considering it tested that way in 300
generations. Epigenetic changes are complex, and it is rare to find ones that
can last for more than a few lifecycles, making it difficult to
study. Thus, using a tool like mating-induced RNA
silencing opens the door for exploring the details of epigenetic
inheritance like never before.
Still, not all genes can be studied this way, as most will
usually recover from silencing and become expressed in future generations. At
the same time, it has now become clear that some genes are vulnerable to
permanent epigenetic changes.
The main takeaways from this study are that mating can be used
to easily induce long-lasting epigenetic modifications, and the occurrence of
this phenomenon happens at the single-gene level.
As Jose put it, “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 heritable epigenetic
While more research is needed to identify other genes vulnerable
to long-lasting epigenetic changes, the team is hopeful that future scientists
will have a clearer understanding of epigenetic heredity and the biological
processes involved, not just in animal models but in humans as well.
Source: S. Devanapallyet
al. (2021). Mating can initiate
stable RNA silencing that overcomes epigenetic recovery. Nature
Reference: Match matters: The right combination
of parents can turn a gene off indefinitely University of
Maryland, College of Computer, Mathematical, and Natural Sciences. July 9,
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