Science classes teach that an individual’s traits are mainly encoded in their genetic sequence—or DNA—which then gets transcribed into RNA that subsequently gets translated into the proteins that carry out cellular functions. But while this is generally true for the majority of traits, it does not account for how all characteristics are passed down across generations. It turns out, epigenetics may play a large role in how traits are inherited.
Researchers at Princeton’s Department of Molecular Biology and the Lewis-Sigler Institute for Integrative Genomics became intrigued by how the nematode C. elegans seemed to pass avoidance behavior towards specific pathogens down across a finite set of generations before the trait would reset. Not all pathogens triggered such a response, and so they focused on studying the one they knew did: Pseudomonas aeruginosa. After encountering the pathogen and learning to avoid it, C. elegans‘ avoidance is transferred across four generations before completely resetting, so that any further resistance must be reacquired via exposure.
A simple experiment in nematodes spoke volumes on epigenetics.
C. elegans were exposed to one of two common pathogens—Pseudomonas aeruginosa or Serratia marcescens—with both of these pathogens triggering avoidance behaviors upon nematode exposure. However, only Pseudomonas aeruginosa saw inherited avoidance across generations, suggesting that this is a pathogen-specific mechanism and not a universal response. Comparison of male and female germlines revealed that both were capable of transmitting the avoidance.
Skeptics might argue that perhaps the developing progeny might have been exposed to the pathogen before being born. But the avoidance behavior did not simply last across mother and child; it endured over four total generations, implicating some other process for transmission.
Analysis of gene transcription profiles of wild-type and exposed mothers and progeny showed a large number of differences in immunity, metabolism, and regulation of gene expression—not just posttranslational modifications but also epigenetics. Changes in complex histone modifications—which alter how DNA is wound around histone proteins or unwound and “exposed” for translation into RNA—were detected alongside changes in the small RNA regulators needed to generate the desired proteins. Specifically, the PRG-1/Piwi 22G siRNA pathway was found to direct the epigenetic modifications that conferred transgenerational inheritance of pathogenic avoidance. By modifying the chromatin, this pathway affects how “accessible” the genetic material is for the cell’s translational and transcriptional processes.
Epigenetic modifications factor in the critical element of timescale.
Epigenetic changes are just one part of the nematode’s response to Pseudomonas aeruginosa exposure, accompanied by an immediate upsurge in immune function to help stave off any potential illness and even death. Avoidance of this particular pathogen has been shown to directly promote C. elegans survival, and so conferring this avoidance across multiple generations supports future progeny that in turn can help keep the species alive.
Knowing how important survival is, then, why is this avoidance not hard-wired into C. elegans?
The answer lies in looking at the Pseudmonas genus. Although Pseudomonas aeruginosa can be a destructive pathogen for C. elegans, some Pseudomonas are actually a source of nutrition; in fact, at low temperatures, even Pseudomonas aeruginosa can be a food source—it’s only at higher temperatures that it becomes truly dangerous. It has also been demonstrated that C. elegans trained to avoid pathogenic Pseudomonas also avoid the less pathogenic ones. Consider how detrimental it would be if C. elegans were to have an entire category of potential food sources immediately ruled out, particularly if they encounter a hostile or otherwise stressed environment.
Flexibility and adaptation pave the way of the future.
Transferring this avoidance across a few generations allows for C. elegans to survive, while also remaining flexible and adaptive to conditions and evolving needs over time. This sort of long-term flexibility in adaptation in turn promotes survival of the species. Although this research was a major step in the right direction, further study of such epigenetic survival machinery needs to be conducted to further characterizes the processes at play not just in a relatively simple model organism like C. elegans, but ultimately within the complex systems of more complex organisms such as humans.
Source: Moore, Rebecca S, et al. “Piwi/PRG-1 Argonaute and TGF-β Mediate Transgenerational Learned Pathogenic Avoidance.” Cell, U.S. National Library of Medicine, 13 June 2019
Reference: Caitlin Sedwick “Danger avoidance can be genetically encoded for four generations” Discovery Princeton News. 6 June 2019. Web.