What’s the News: We’ve long had signs that when it comes to inheritance, DNA isn’t the be-all, end-all. Trees that have the exact same genes but were raised in different greenhouses behave differently. Worms with genes that impart long life can pass on that longevity to their progeny—even if they don’t pass on the genes. Both of these phenomena, we’ve discovered, come from epigenetic changes in tags attached to DNA that control whether genes get expressed.
But every now and then we get a whiff of other possible routes for inheritance, even stranger than that. A new paper in Cell reports that worms whose grandparents had the ability to fight viruses using a fleet of tiny RNA molecules retain these molecules even when they don’t have the genes for them. They can pass these molecules down for more than a hundred generations.
What They Saw:
- This team engineered worms that didn’t have the genes to make the RNAs—which work by gumming up viruses’ replication machinery—and then bred them with worms that did for several generations. They ended up with some worms whose ancestors had had the virus-fighting molecules, but did not themselves possess the necessary genes.
- The team then watched these worms under the microscope and saw that they still attacked viruses in exactly the same way as their grandparents. Numerous control experiments confirmed that the effect was real, and only happened in worms who had ancestors with the genes. The researchers collected all the various RNA molecules in these worms and saw that indeed, they possessed the virus-fighting variety.
- After about three generations, the effect seemed to wear off; most worms without the genes stopped being able to attack viruses. But for some worms, it never stopped. The team bred those worms for more than one hundred generations, nearly a year, and the creatures never flagged in their ability to defend themselves.
How the Heck:
- How is this possible? The team keeps mum on any ideas of how this inheritance works. But they do uncover some tantalizing details that give us room for speculation. One possibility is that the RNA molecules made by the original worms in response to a virus attack were floating around in the cytoplasm of the eggs and sperm that became their offspring. If that’s the case, then the offspring are basically using their parents’ leftovers, with each generation having a bit less of the original stuff. The researchers mention this possibility of the original RNA being “diluted” with each generation, but don’t, as far as we can tell, try to test that.
- But what about the worms that hang on to the RNA indefinitely? The researchers found that for that to happen, a particular enzyme that builds RNAs has to be present. Maybe, then, these worms manage to jerry-rig a way to make copies of the virus-fighting RNA with that enzyme (which isn’t part of the usual machinery), even though they lack the gear required to make it in the normal fashion. The gene for that enzyme would then be passed on as normal.
The Future Holds:
- This work raises a number of questions, and doesn’t provide many clear answers. But the conundrum of how traits can be passed down without the use of DNA is perennially fascinating, and there are a number of clear follow-up experiments that this team didn’t pursue. Here’s hoping other researchers will shed light on how these worms manage to do it.
- In the meantime, this team is planning new experiments to see if RNA inheritance is involved in other traits. Specifically, they are looking to replicate in worms a famous case of epigenetic inheritance: the Dutch famine during World War II, which was linked to higher rates of obesity in several generations following. This effect has been attributed to alterations in the chemical tags on DNA, but the team is interested in seeing whether RNA inheritance also plays a role.
Reference: Oded Rechavi, Gregory Minevich, Oliver Hobert. Transgenerational Inheritance of an Acquired Small RNA-Based Antiviral Response in C. elegans. Cell, 2011; DOI: 10.1016/j.cell.2011.10.042
Image courtesy of PLoS, via Wikimedia Commons