Does Yolk Post-Translational Modification Contribute to Generational Inheritance of Acquired Traits?

Research into epigenetic and non-genetic inheritance has benefited tremendously from the model nematode C. elegans. However, for historical reasons, most discoveries were made in the context of studying RNA and its role in regulating gene expression. Recent publications indicate that non-genetic inheritance may be influenced by environmental factors and variables. One such variation, starvation-induced developmental arrest in C. elegans, has been shown to result in transgenerational genetic changes inherited over three consecutive generations [Rechavi et al., 2014]. Furthermore, new evidence suggests that proposed adaptive and deleterious intergenerational effects are molecularly related at the level of gene expression [Burton et al., 2021].

This project investigates non-genetic inheritance by altering various parameters associated with C. elegans maintenance, aiming to identify unique generational proteins that act as transduction factors relaying signals from parent to offspring. Protein identification will be based on the presence of post-translational modifications associated with unique parameters, such as variations in diet, temperature, the presence of male worms, and exposure to pathogenic bacteria. Identified pathways will be assessed for inter-generational and trans-generational properties. One proposed mechanism for non-genetic inheritance is signaling between parental and embryonic yolk proteins. Profiling of post-translational modifications (PTMs) will be performed using mass spectrometry to further investigate this hypothesis.

Protein structures were created using AlphFold 3. PTMs were extracted from uniport.org and Li et al., “Insulin signaling regulates longevity through protein phosphorylation in Caenorhabditis elegans.” 2021 Nature Communications. 

Protein interactions were obtained from biogrid.org. 

Burton NO, et al. Intergenerational adaptations to stress are evolutionarily conserved, stress-specific, and have deleterious trade-offs. Elife. 2021 Oct 8;10:e73425. PMID: 34622777

Rechavi O, et al. Starvation-induced transgenerational inheritance of small RNAs in C. elegans. Cell. 2014 Jul 17;158(2):277-287. PMID: 25018105

Krebs NF, et al. Infant factors that impact the ecology of human milk secretion and composition-a report from "Breastmilk Ecology: Genesis of Infant Nutrition (BEGIN)" Working Group 3. Am J Clin Nutr. 2023 May 10;117 Suppl 1(Suppl 1):S43-S60. PMID: 37173060