Piwi/PRG-1 Argonaute and TGF-β Mediate Transgenerational Learned Pathogenic Avoidance

Abstract

The ability to inherit learned information from parents could be evolutionarily beneficial, enabling progeny to better survive dangerous conditions. We discovered that, after C. elegans have 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-b 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 avoidancebased 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.

Proximate causes and consequences of intergenerational influences of salient sensory experience

“…Many cases of such intergenerational influences of sensory environments arise via social transmission through maternal behavior and via the transfer of chemical cues across maternal‐fetal barriers or egg barriers in viviparous or oviparous species, respectively . While there is accumulating evidence that intergenerational influences of sensory environments are observed in offspring of worms, fruit flies and mice that were not conceived at the time of parental exposure to salient sensory stimuli, mechanisms underlying these influences are unknown. To the best of our knowledge, our study is the first to show that RNA found in the male germline of mammals exposed to salient olfactory experience can contribute to impacting olfactory‐related neuroanatomy and function in future generations.…”

“…Odor‐based learning has been shown to have intergenerational effects in offspring . Most recently, the effects of aversive taste conditioning in a parental generation have been reported to persist in at least four generations of worms . Building on our studies using olfactory fear conditioning in a parental generation of mice and examining influences in offspring, we ask how intergenerational influences of salient olfactory experiences can be inherited across generations and what consequence such influences have on the behavior of the offspring as they navigate their own umwelts.…”

A Waddington Epigenetic Landscape for the C. elegans embryo

“…Transgenerational behavior genes contribute to the modeled landscape The enrichment in genes that regulate transgene silencing, stress response and behavior among the top tensors of the early epigenetic landscape, suggested that early embryogenesis is shaped by the physiological adaptations of parents. Indeed, genes upregulated or downregulated in the progeny of animals that were fed pathogenic bacteria (PA14) were enriched in top tensors (p-value = 1.572e-07 and 6.960e-14, respectively Table 2 and Methods) (Moore et al, 2019). This was not the case for genes that continued to be regulated in the following generation (F2) ( Table 2).…”

“…However, with the discovery of RNAi and the inheritance of endogenous small RNAs and their accompanying protein argonautes, an alternative path to inherited adaptations has been uncovered (Buckley et al, 2012;Fire et al, 1998). These forms of transgenerational epigenetic inheritance provide the benefits of an adaptation to individuals before it is genetically fixed in a population (Buckley et al, 2012;Fire et al, 1998;Moore et al, 2019;Posner et al, 2019).…”

“…Pseudomonas aeruginosa -PA14), worms adapt by developing and remembering an aversion to food (Zhang et al, 2005). Moreover, this behavioral adaptation can be transmitted from mothers to their progeny in a manner dependent on the germline argonaute Piwi/PRG-1 and its piRNAs (Moore et al, 2019). PRG-1 and piRNAs are necessary for germline development and guard its integrity by silencing of transposable elements and foreign nucleic acids Batista et al, 2008;Ghildiyal and Zamore, 2009;Lee et al, 2012;Shirayama et al, 2012).…”