title: The Drosophila transcriptional network is structured by microbiota.
abstract: Resident 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.
  
  
  
  Our 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.
  
  
  
  Our 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.
authors.affiliation: Department of Entomology, Cornell University, Ithaca, NY, USA.|Present address: Institute of Healthy Ageing, Department of Genetics Evolution and Environment, University College London, Gower Street, London, WC1E 6BT, UK.
authors.forename: Adam J
authors.initials: AJ
authors.lastname: Dobson
authors.affiliation: Department of Entomology, Cornell University, Ithaca, NY, USA.|Present address: Department of Plant and Wildlife Sciences, Genetics and Biotechnology, Brigham Young University, Provo, UT, 84602, USA.
authors.forename: John M
authors.initials: JM
authors.lastname: Chaston
authors.affiliation: Department of Entomology, Cornell University, Ithaca, NY, USA. aes326@cornell.edu.|Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY, USA. aes326@cornell.edu.
authors.forename: Angela E
authors.initials: AE
authors.lastname: Douglas
mesh_terms: D000818:Animals; D004331:Drosophila melanogaster / Q000235:genetics* / Q000382:microbiology* / Q000502:physiology; D020869:Gene Expression Profiling; D053263:Gene Regulatory Networks; D064307:Microbiota; D013559:Symbiosis
keywords: Coexpression; Drosophila; Gene regulation; Microbiota; Symbiosis; Transcriptional network