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

Background Heligmosomoides bakeri (often mistaken for 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. Methods We
generated biologically replicated RNA-seq datasets from samples taken
throughout the parasitic life of H. bakeri. RNA from tissue-dwelling and
lumen-dwelling worms, collected under a dissection microscope, was
sequenced on an Illumina platform. Results 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. We find
sex-linked differences in transcription related to aging and oxidative and
osmotic stress responses. We observe a starvation-like signature among
transcripts whose expression is consistently upregulated 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. Furthermore, 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. Conclusions We examine how different the male and
female worms are at the molecular level and describe major developmental
events that occur in the worm, which extend our understanding of the
interactions between this parasite and its host. In addition to generating
new hypotheses for follow-up experiments into the worm’s behavior,
physiology, and metabolism, our datasets enable future more in-depth
comparisons between nematodes to better define the utility of H. bakeri as
a model for parasitic nematodes in general.