Match matters: The right combination of parents can turn a gene off indefinitely

Date:
July 9, 2021
Source:
University of Maryland
Summary:
A new study provides a potential tool for unraveling the mystery
of how experiences can cause inheritable changes to an animal's
biology. By mating nematode worms, they produced permanent
epigenetic changes that lasted for more than 300 generations.



FULL STORY ========================================================================== Evidence suggests that what happens in one generation -- diet,
toxin exposure, trauma, fear -- can have lasting effects on future
generations. Scientists believe these effects result from epigenetic
changes that occur in response to the environment and turn genes on or
off without altering the genome or DNA sequence.


==========================================================================
But how these changes are passed down through generations has not been understood, in part, because scientists have not had a simple way to
study the phenomenon. A new study by researchers at the University of
Maryland provides a potential tool for unraveling the mystery of how experiences can cause inheritable changes to an animal's biology. By
mating nematode worms, they produced permanent epigenetic changes that
lasted for more than 300 generations. The research was published on July
9, 2021, in the journal Nature Communications.

"There's a lot of interest in heritable epigenetics," said Antony Jose, associate professor of cell biology and molecular genetics at UMD and
senior author of the study. "But getting clear answers is difficult. For instance, if I'm on some diet today, how does that affect my children and grandchildren and so on? No one knows, because so many different variables
are involved. But we've found this very simple method, through mating,
to turn off a single gene for multiple generations. And that gives us
a huge opportunity to study how these stable epigenetic changes occur."
In the new study, Jose and his team found while breeding nematode worms
that some matings led to epigenetic changes in offspring that continued
to be passed down through as many generations as the scientists continued
to breed them.

This discovery will enable scientists to explore how epigenetic changes
are passed to future generations and what characteristics make genes susceptible to permanent epigenetic changes.

Jose and his team began this work in 2013, while working with nematode
worms, Caenorhabditis elegans (C. elegans), a species often used as a
model for understanding animal biology. The scientists noticed that worms
bred to carry a gene they called T, which produces fluorescent proteins, sometimes glowed and sometimes didn't. This was puzzling because the
glowers and the non-glowers had nearly identical DNA.

"Everything began when we stumbled upon a rare gene that underwent
permanent change for hundreds of generations just by mating. We could
have easily missed it," said Sindhuja Devanapally (Ph.D. '18, biological sciences), a co-lead author of the study who is now a postdoctoral fellow
at Columbia University.



==========================================================================
To understand the phenomenon better, the researchers conducted breeding experiments in which only the mother or the father carried the fluorescent gene. The team expected that no matter which parent carried the gene,
the offspring would glow. Instead, they found that when the mother
carried the fluorescent gene, the offspring always glowed, meaning
the gene was always turned on. But when the father carried the gene,
the offspring usually weakly glowed or did not glow at all.

"We found that there are these RNA-based signals controlling gene
expression," Jose said. "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." When the
silencing signal wins, the gene is silenced for good, or for at least
300 generations, which is how long Jose and his colleagues followed their laboratory-bred worms. Previous examples of epigenetic changes were more complex or they did not last more than a couple of generations. The
researchers don't yet know why the silencing signal only wins some of
the time, but this new finding puts them in a much better position to
explore the details of epigenetic inheritance than ever before.

"While we've found a set of genes that can be silenced almost permanently,
most other genes are not affected the same way," said the study's other
co-lead author, Pravrutha Raman (Ph.D. '19, biological sciences),
who is now a postdoctoral fellow at Fred Hutchinson Cancer Research
Center. "After silencing, they bounce back and become expressed in future generations." With their new findings, the researchers now believe some
genes could be more vulnerable to permanent epigenetic change while other
genes recover within a few generations. Although studies in worms are
not the same as in humans, the research provides a window into biological processes that are likely shared, at least in part, by all animals.

"The two big advantages we now have from this work are that this
long-lasting epigenetic change is easy to induce through mating, and
that it occurs at the level of a single gene," 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 heritable epigenetic change." Jose and his colleagues expect that
future studies may one day help scientists identify human genes that
are vulnerable to long-lasting epigenetic changes.

========================================================================== Story Source: Materials provided by University_of_Maryland. Note:
Content may be edited for style and length.


========================================================================== Journal Reference:
1. Sindhuja Devanapally, Pravrutha Raman, Mary Chey, Samual Allgood,
Farida
Ettefa, Mai"gane Diop, Yixin Lin, Yongyi E. Cho, Antony
M. Jose. Mating can initiate stable RNA silencing that overcomes
epigenetic recovery.

Nature Communications, 2021; 12 (1) DOI: 10.1038/s41467-021-24053-4 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2021/07/210709094505.htm

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