Transcriptional patterns of sexual dimorphism and host developmental programs in the model parasitic nematode Heligmosomoides polygyrus

Heligmosomoides polygyrus is a promising model for parasitic nematodes with the key advantage of being amenable to study and manipulation within a controlled laboratory environment. While draft genome sequences are available for this worm, which allow for comparative genomic analyses between nematodes, there is a notable lack of information on its gene expression. Here, we have generated biologically replicated RNA-seq datasets from samples taken throughout the parasitic life of H. polygyrus. We find extensive transcriptional sexual dimorphism throughout the fourth larval and adult stages of this parasite and identify alternative splicing, glycosylation, and ubiquitination as particularly important processes for establishing and/or maintaining sex-specific gene expression in this species. Further, we find sex-linked differences in transcription related to aging and oxidative and osmotic stress responses. Additionally, we observe a starvation-like signature among transcripts whose expression is consistently up-regulated in males, which may reflect a higher energy expenditure by male worms. We detect evidence of increased importance for anaerobic respiration among the adult worms, which coincides with the parasite's migration into the physiologically hypoxic environment of the intestinal lumen. Further, we hypothesize that oxygen concentration may be an important driver of the worms encysting in the intestinal mucosa as larvae, which not only fully exposes the worms to their host's immune system, but also shapes many of the interactions between the host and parasite. We find stage- and sex-specific variation in the expression of immunomodulatory genes and in anthelmintic targets. In addition to generating new hypotheses for follow-up experiments into the worm's behaviour, physiology, and metabolism, our datasets enable future more in-depth comparisons between nematodes to better define the utility of H. polygyrus as a model for parasitic nematodes in general. ### Competing Interest Statement The authors have declared no competing interest.