Transgenerational Effects of Extended Dauer Diapause on Starvation Survival and Gene Expression Plasticity in Caenorhabditis elegans

Abstract

Phenotypic plasticity is facilitated by epigenetic regulation, and remnants of such regulation may persist after plasticityinducing cues are gone. However, the relationship between plasticity and transgenerational epigenetic memory is not understood. Dauer diapause in Caenorhabditis elegans provides an opportunity to determine how a plastic response to the early-life environment affects traits later in life and in subsequent generations. We report that, after extended diapause, postdauer worms initially exhibit reduced reproductive success and greater interindividual variation. In contrast, F3 progeny of postdauers display increased starvation resistance and lifespan, revealing potentially adaptive transgenerational effects. Transgenerational effects are dependent on the duration of diapause, indicating an effect of extended starvation. In agreement, RNA-seq demonstrates a transgenerational effect on nutrient-responsive genes. Further, postdauer F3 progeny exhibit reduced gene expression plasticity, suggesting a trade-off between plasticity and epigenetic memory. This work reveals complex effects of nutrient stress over different time scales in an animal that evolved to thrive in feast and famine.

Inter-generational consequences for growing Caenorhabditis elegans in liquid

“…We found that the worms' concentration in liquid affects their size ( p , 0.0001, one-way ANOVA), and that while in low concentrations, the liquid-grown worms are longer (figure 1b,c); in very high concentrations, liquid-grown worms become shorter (perhaps in this condition, not enough food is available). As starvation is known to generate heritable effects in C. elegans [8][9][10][11], in all the subsequent experiments, we grew worms in liquid in low concentrations (maximum 0.05 worms per microlitre, see Methods). In this concentration, liquid-grown worms are approximately 22% longer than plate-grown worms ( p , 0.0001, Sidak's multiple comparisons test, figure 1b,c).…”

“…Previously, certain environmental stresses, such as L1 starvation [8], starvation during dauer arrest [11] and exposure to high temperatures [12], were shown to induce transgenerational effects that persist for more than two generations. To test whether the elongated body morphology can be inherited for more than one generation, we measured the body length of plate-grown worms that derive from liquid-grown parents in the F1, F2 and F3 generations.…”

“…However, in Caenorhabditis elegans, substantial understanding has been gained regarding the molecular mechanisms that allow transmission of responses via small RNAs across multiple generations (reviewed in [4]). Further, many studies with C. elegans have demonstrated that different environmental challenges leave a trace in the progeny, for example, viral infections [5][6][7], starvation [8][9][10][11], high temperatures [12][13][14], high osmolality [15,16] and exposure to toxins [15]. Such stressors can lead to short-or long-term gene expression alterations and physiological changes.…”

AMPK regulates germline stem cell quiescence and integrity through an endogenous small RNA pathway

“…How this modification in transcriptional output provides some adaptive advantage has not yet been unequivocally determined, but animals that transit through dauer live longer and have a significantly higher brood size (11). These changes may be heritable since animals that remain in dauer for extended periods also show significant alterations in their gene expression, while also demonstrating and enhanced resistance to starvation in subsequent generations (38). Therefore, the dauer larva may be a perfect example of how perceived environmental duress is transduced to the germ line.…”

Neuronal perception of the social environment intergenerationally controls germline development and generation time inC. elegans

“…It remains unclear how most of these phenomena relate to physiological intergenerational plastic responses to natural environments (Perez and Lehner 2019). However, recent reports of multigenerational effects of the environment on stress resistance and life history traits (Burton et al 2017, Hibshman et al 2016, Jobson et al 2015, Webster et al 2018, Palominos et al, 2017, on behavioral avoidance of pathogenic bacteria (Kaletsky et al 2019 and on pathogen resistance (Burton et al, 2020) suggest that non-genetic inheritance in C. elegans may indeed have ecological significance.…”