Transmitting Learned Behavior to Future Generations (in Worms)

Parents pass along DNA, RNA, proteins and all the contents of cytoplasm directly to their offspring, but not memories. So parental experiences don’t directly inform the behavior of their children… unless those children are roundworms. Two recent papers describe mechanisms that allow parental experiences to be transmitted to their offspring, sometimes for several generations, in the roundworm Caenorhabditis elegans ( C.elegans — nobody says the full name). In both cases transgenerational behavior effects were dependent on small RNA populations, adding another function to the already diverse set of roles that RNA can accomplish. There is no evidence that other species, especially large complex ones like humans, exhibit anything like these mechanisms—but these papers have created a legitimate avenue of investigating if similar pathways exist in other animals and how the experiences of the parents might directly effect the behavior of their offspring.

Longer summaries can be found in the Neuroscience News and Science Daily, and summaries and links to the two original articles are listed below. Neither article is easy reading but the summaries are pretty good.

Posner et al. (2019) Neuronal Small RNAs Control Behavior Transgenerationally. Cell

Summary

It is unknown whether the activity of the nervous system can be inherited. In Caenorhabditis elegans nematodes, parental responses can transmit heritable small RNAs that regulate gene expression transgenerationally. In this study, we show that a neuronal process can impact the next generations. Neurons-specific synthesis of RDE-4-dependent small RNAs regulates germline amplified endogenous small interfering RNAs (siRNAs) and germline gene expression for multiple generations. Further, the production of small RNAs in neurons controls the chemotaxis behavior of the progeny for at least three generations via the germline Argonaute HRDE-1. Among the targets of these small RNAs, we identified the conserved gene saeg-2, which is transgenerationally downregulated in the germline. Silencing of saeg-2 following neuronal small RNA biogenesis is required for chemotaxis under stress. Thus, we propose a small-RNA-based mechanism for communication of neuronal processes transgenerationally.

Moore et al. (2019) Piwi/PRG-1 Argonaute and TGF-β Mediate Transgenerational Learned Pathogenic Avoidance. Cell

Summary

The ability to inherit learned information from parents could be evolutionarily beneficial, enabling progeny to better survive dangerous conditions. We discovered that, after C. eleganshave learned to avoid the pathogenic bacteria Pseudomonas aeruginosa (PA14), they pass this learned behavior on to their progeny, through either the male or female germline, persisting through the fourth generation. Expression of the TGF-β ligand DAF-7 in the ASI sensory neurons correlates with and is required for this transgenerational avoidance behavior. Additionally, the Piwi Argonaute homolog PRG-1 and its downstream molecular components are required for transgenerational inheritance of both avoidance behavior and ASI daf-7 expression. Animals whose parents have learned to avoid PA14 display a PA14 avoidance-based survival advantage that is also prg-1 dependent, suggesting an adaptive response. Transgenerational epigenetic inheritance of pathogenic learning may optimize progeny decisions to increase survival in fluctuating environmental conditions.