Roundworms do inherit info on threats to avoid, but with a catch

Animals often meet the same threats across generations. A central question in biology is whether experience with a threat can be passed from parents to offspring in a way that changes the latter’s behaviour.

In the roundworm Caenorhabditis elegans, one such experience is learning to avoid a dangerous bacterium called Pseudomonas aeruginosa strain PA14. Previous work has suggested that worms exposed to PA14 can produce descendants that also avoid this bacterium, even though those descendants have never encountered it. Other researchers, however, reported that this inherited avoidance didn’t reliably persist beyond the first generation, casting doubt on the phenomenon.

A new study by researchers from Illinois State University in the US was designed to address this disagreement with an independent replication study. Working in a different laboratory, they closely followed the previous study’s protocol and focused on whether learned avoidance could still be detected in the second generation, where previous results began to diverge.

The authors used a standard choice assay. The worms were placed on a plate where one spot contained their usual lab food, a harmless Escherichia coli strain called OP50, and another spot contained the pathogenic PA14. A compound called sodium azide was added to each spot to paralyse worms as soon as they arrived, so their first choice could be recorded. Worms were first ‘trained’ by spending 24 hours on PA14 or OP50, and then their preference, and that of their offspring and the offspring’s offspring raised only on OP50, was tested in the assay.

Naïve worms that had never seen PA14 showed the expected initial attraction to the pathogen over OP50. After training on PA14, however, parental worms strongly avoided PA14 in the choice assay. Crucially, their descendants, which had never themselves encountered PA14, also shifted to avoiding the pathogen compared to control worms whose ancestors had only seen OP50. The inherited effect weakened with each generation but remained statistically significant in the second generation descendants when the assay was run in tightly controlled conditions.

The findings were published in eLife on November 11. A companion article by Canada’s Michael G. DeGroote Institute for Infectious Disease Research associate professor Lesley MacNeil, who wasn’t involved in the studies, placed the findings in a broader debate about “transgenerational epigenetic inheritance”. Dr. MacNeil contrasted the old and new study with a third set of studies that often didn’t detect either the initial attraction to PA14 or its inherited avoidance when using a different method that immobilised worms by cooling the plate instead of using azide. This alternative method could have allowed the worms to contact PA14 during the assay and learn on the spot, blurring the difference between naïve and previously trained lineages.

Taken together, the first two papers (i.e. old and new) strengthen the case that signals from microbes, including small RNAs produced by PA14, can leave heritable marks that shape how C. elegans descendants respond to future threats. At the same time, comparing their findings with the third line of inquiry underlines that claims about such inheritance must rest on protocols that others can reproduce and scrutinise.