Abstract
BackgroundResident microorganisms (microbiota) have far-reaching effects on the biology of their animal hosts, with major consequences for the host’s health and fitness. A full understanding of microbiota-dependent gene regulation requires analysis of the overall architecture of the host transcriptome, by identifying suites of genes that are expressed synchronously. In this study, we investigated the impact of the microbiota on gene coexpression in Drosophila.ResultsOur transcriptomic analysis, of 17 lines representative of the global genetic diversity of Drosophila, yielded a total of 11 transcriptional modules of co-expressed genes. For seven of these modules, the strength of the transcriptional network (defined as gene-gene coexpression) differed significantly between flies bearing a defined gut microbiota (gnotobiotic flies) and flies reared under microbiologically sterile conditions (axenic flies). Furthermore, gene coexpression was uniformly stronger in these microbiota-dependent modules than in both the microbiota-independent modules in gnotobiotic flies and all modules in axenic flies, indicating that the presence of the microbiota directs gene regulation in a subset of the transcriptome. The genes constituting the microbiota-dependent transcriptional modules include regulators of growth, metabolism and neurophysiology, previously implicated in mediating phenotypic effects of microbiota on Drosophila phenotype. Together these results provide the first evidence that the microbiota enhances the coexpression of specific and functionally-related genes relative to the animal’s intrinsic baseline level of coexpression.ConclusionsOur system-wide analysis demonstrates that the presence of microbiota enhances gene coexpression, thereby structuring the transcriptional network in the animal host. This finding has potentially major implications for understanding of the mechanisms by which microbiota affect host health and fitness, and the ways in which hosts and their resident microbiota coevolve.Electronic supplementary materialThe online version of this article (doi:10.1186/s12864-016-3307-9) contains supplementary material, which is available to authorized users.
Highlights
Resident microorganisms have far-reaching effects on the biology of their animal hosts, with major consequences for the host’s health and fitness
To address the extent to which gene coexpression of the Drosophila transcriptional network is microbiota-dependent, we devised a gene coexpression metric, the distribution of which reflects the tendency of pairs of transcripts to be co-regulated (0 = no co-regulation, 1 = perfect co-regulation), and calculated it for all gene-gene pairs in the transcriptome
The distribution of the coexpression metric differed between axenic and gnotobiotic flies (Kolmogorov-Smirnov test D = 0.0191, p < 2.2e-16), and median transcriptome-wide coexpression was reduced in axenic flies relative to gnotobiotic flies (Wilcoxon rank-sum test W = 3.1e16, p < 2.2e-16), suggesting that microbiota promotes structure in the Drosophila transcriptional network
Summary
Resident microorganisms (microbiota) have far-reaching effects on the biology of their animal hosts, with major consequences for the host’s health and fitness. Differential coexpression analysis (DiffCoEx) identifies modules of genes that show similar changes in coexpression (either relative to each other, relative to the rest of the transcriptome, or both) between conditions, isolating regulatory patterns that are altered or preserved. This approach recognizes that the expression of any one gene is potentially subject to reciprocal interactions from any other gene in the transcriptome, and mechanisms that govern the expression of many genes (e.g., transcription factors, chromatin modifications, DNA methylation). Microbial influence on the host at this gene regulatory level would be consistent with ancient origins of hostmicrobe interactions
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