Insights into the genetic basis of early-life starvation-induced germline abnormalities in C. elegans

Abstract

Humans subjected to starvation early in development are especially prone to a wide variety of diseases such as cancer, hypertension, and cardiovascular disease later in life. Here, we use the model system C. elegans in order to better understand resistance and responses to starvation stress. By elucidating some of the mechanisms involved in starvation responses, we can better understand and address diseases associated with early malnutrition in humans. Candidate genes were identified via RNAseq of wild-type worms that had been starved for 1 (d1) and 8 days (d8). glp-1/Notch, gld-1/Quaking, and cep-1/p53 were all identified as likely regulators of tumorigenesis involved in the starvation response. glp-1 loss-of-function mutants reduced tumorigenesis rates in the d8 group while the glp-1 gain-of-function mutant showed no epistatic interaction. Both the gld-1 and cep-1 mutants demonstrated an increase in tumorigenesis rates in the d8 group. Additionally, three wild isolate strains, ED3077, CB4856, and JU561 were compared to N2 to determine the presence of natural variation in starvation resistance. Each strain was split into d1 and d8 groups, and starvation resistance was assessed through relative fecundity. ED3077 showed no difference in d1 and d8 brood size, which leads to speculation that ED3077 has differential activity of the aforementioned genes, conferring resistance to early-life starvation-induced pathology.