Maryland: The basics of genetic inheritance are well known: parents each pass half
of their DNA to their offspring during reproduction. This genetic
recipe is thought to contain all of the information that a new organism
needs to build and operate its body. But recent research has
shown that, in some species, parents’ life experiences can alter their
offspring. Being underfed, exposed to toxins or stricken by disease can
cause changes in a parent’s gene expression patterns, and in some cases,
these changes can be passed down to the next generation. However, the
mechanisms that cause this effect—known as non-genetic inheritance—are a
mystery.
New research from the University of Maryland provides a
surprising possible explanation. For the first time, developmental
biologists have observed molecules of double-stranded RNA (dsRNA)—a
close cousin of DNA that can silence genes within cells—being passed
directly from parent to offspring in the roundworm Caenorhabditis
elegans. Importantly, the gene silencing effect created by dsRNA
molecules in parents also persisted in their offspring.
The work, published October 17, 2016 in the online early edition of the
Proceedings of the National Academy of Sciences, suggests that the
mechanisms for non-genetic inheritance might be simpler than anyone had
suspected.
“This is the first time we’ve seen a dsRNA molecule
passing from one generation to the next,” said Antony Jose, an assistant
professor in the UMD Department of Cell Biology and Molecular Genetics
and senior author on the study. “The assumption has been that dsRNA
changes the parent’s genetic material and this altered genetic material
is transmitted to the next generation. But our observations suggest that
RNA is cutting out the middle man.”
Jose and his team, including
graduate student and lead author Julia Marré and former research
technician Edward Traver, introduced dsRNA marked with a fluorescent
label into the circulatory system of C. elegans worms. They then watched
as these fluorescent RNA molecules physically moved from the parent’s
circulatory system into an egg cell waiting to be fertilized.
In
a surprising turn of events, some of the dsRNA molecules could not
silence genes in the parent because the dsRNA sequence did not match any
of the parent’s genes. But the dsRNA molecules did silence genes in the
offspring, when the new worm gained a copy of the matching gene from
its other parent. This suggests that, in some cases, gene silencing by
dsRNA might be able to skip an entire generation.
“It’s shocking
that we can see dsRNA cross generational boundaries. Our results “But
it’s doubly surprising to see that a parent can transmit the information
to silence a gene it doesn’t have.”
Jose and his colleagues did
not expect dsRNA to play such a direct role in the transmission of
information across generations. Because dsRNA factors into the life
cycle of many viruses, Jose explained, it is reasonable to assume that a
living cell’s natural defenses would prevent dsRNA from invading the
next generation.
“It’s very surprising. One would think the next
generation would be protected, but we are seeing all of these dsRNA
molecules being dumped into the next generation,” Jose added. “Egg cells
use the same mechanism to absorb nutrients as they prepare for
fertilization. The next generation is not only getting nutrition, it’s
also getting information.”
Jose and his colleagues hope to learn
more about the precise mechanisms by which dsRNA silences genes across
multiple generations.
“There are hints that similar things could
be happening in humans. We know that RNA exists in the human
bloodstream. But, we don’t know where the RNA molecules are coming from,
where they’re going or exactly what they’re doing,” Jose said. “Our
work reveals an exciting possibility—they could be messages from parents
to their offspring.”
In addition to Jose, UMD co-authors on the
paper included graduate student Julia Marré and former research
technician Edward Traver.