Biologists first to observe direct inheritance of gene-silencing RNA

October 17, 2016
In this image of a roundworm (Caenorhabditis elegans), a recently fertilized egg cell (arrow) contains particles of double-stranded RNA (dsRNA, small magenta dots) that are capable of silencing specific genes. A new University of Maryland study shows, for the first time, that these dsRNA molecules pass directly from the parent worm's circulatory system to the egg, revealing a possible mechanism for non-genetic inheritance. Credit: Antony Jose

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 , and in some cases, these changes can be passed down to the next . 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 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.

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In this sequence of microscopic images, taken at the University of Maryland, an immature egg cell from the roundworm Caenorhabditis elegans gets ready for fertilization. The egg already contains half the DNA needed to create a new worm. But as it picks up nutrients from its parent, the egg also picks up particles of double-stranded RNA -- seen here as small magenta dots. This marks the first time that scientists have directly observed particles of double-stranded RNA being transferred to a new generation, revealing new details about non-genetic inheritance. Credit: Antony Jose/University of Maryland College of Computer, Mathematical, and Natural Sciences

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 provide a concrete mechanism for how the environment in one generation could affect the next generation," Jose said. "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 to their offspring."

Explore further: New mechanism of inheritance could advance study of evolution, disease treatment

More information: Extracellular RNA is transported from one generation to the next in Caenorhabditis elegans,PNAS, www.pnas.org/cgi/doi/10.1073/pnas.1608959113

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johnhew
5 / 5 (1) Oct 17, 2016
From microbes to man, this nutrient-based instruction of phenotype and genotype makes Lamarck smile a Lamarckian smile.

RealScience
not rated yet Oct 17, 2016
While it certainly is good to see dogma overthrown, and see one mechanism for non-gene-sequence inheritance elucidated, you sound a bit like a JVK-apologist.

First, it is not specifically nutrient-based instruction, it is general instruction, with "exposed to toxins or stricken by disease" already known in addition to "underfed".

Second, so far it has only been shown to be phenotype instruction (including which genes are expressed) and it has not yet (to my knowledge, anyway) been shown to be genotype instruction (altering or instructing the alteration of the gene sequence).

(And third, if you were intentionally sounding JVKish, JVK's problem was not his support of nutrient / pheromone-driven changes, but his insistence that those were the ONLY mechanism for change in species.)

But I agree that it will make Lamarck smile, and that makes me smile because it shows the importance of keeping an open mind rather than subscribing to the dogma-du-jour.

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