Transgenerational Adaptation to Hypoxia

Adaptation to environmental stresses is crucial for survival. Transgenerational epigenetic inheritance allows organisms to respond to irregular conditions, alert their naïve descendants that stresses could still be present, and for distant descendants to eventually return to a basal state after several generations without the stress. However, it is still unclear whether organisms adapt on a transgenerational scale after repeated generational exposures to the same environmental stress. We recently found that C. elegans exposed to hypoxia in the parental (P0) generation: increased longevity in the P0 generation, caused an intergenerational reduction in lipids, and elicited a transgenerational reduction in fertility (P0-F2) that was dependent on small RNAs that were transmitted from parents to their naïve children. Here, we find that exposure of subsequent generations of C. elegans to hypoxia caused a transgenerational adaptation such that C. elegans that had repeated generational exposure to hypoxia failed to display hypoxia induced phenotypes. We show that upon two repeated generational exposures to hypoxia, C. elegans no longer display an increase in lifespan, and after four repeated generational exposures to hypoxia, C. elegans no longer display a decrease in reproduction. Transgenerational adaptation of the reproduction phenotype is dependent on the putative H3K27 trimethytransferase PRC2 complex and we identified critical genes that adapted on a transgenerational timeframe to repeated hypoxia exposure. Our findings reveal that transgenerational adaptation occurs and suggest that H3K27me3 is a critical modification for adapting to repeated generational stresses. To investigate potential genes and mechanisms involved in transgenerational adapatation to hypoxia in C. Elegans, worms and their progeny were exposed to normoxia or hypoxia conditions for 4 generations. Differential gene analysis was performed using data obtained from RNA-seq of C. Elegans after each generation of exposure