Host Genotype and Microbiota Contribute Asymmetrically to Transcriptional Variation in the Threespine Stickleback Gut.

Recent studies of interactions between hosts and their resident microbes have revealed important ecological and evolutionary consequences that emerge from these complex interspecies relationships, including diseases that occur when the interactions go awry. Given the preponderance of these interactions, we hypothesized that effects of the microbiota on gene expression in the developing gut-an important aspect of host biology-would be pervasive, and that these effects would be both comparable in magnitude to and contingent on effects of the host genetic background. To evaluate the effects of the microbiota, host genotype, and their interaction on gene expression in the gut of a genetically diverse, gnotobiotic host model, the threespine stickleback (Gasterosteus aculeatus), we compared RNA-seq data among 84 larval fish. Surprisingly, we found that stickleback population and family differences explained substantially more gene expression variation than the presence of microbes. Expression levels of 72 genes, however, were affected by our microbiota treatment. These genes, including many associated with innate immunity, comprise a tractable subset of host genetic factors for precise, systems-level study of host-microbe interactions in the future. Importantly, our data also suggest subtle signatures of a statistical interaction between host genotype and the microbiota on expression patterns of genetic pathways associated with innate immunity, coagulation and complement cascades, focal adhesion, cancer, and peroxisomes. These genotype-by-environment interactions may prove to be important leads to the understanding of host genetic mechanisms commonly at the root of sometimes complex molecular relationships between hosts and their resident microbes.