title: A whole transcriptomal linkage analysis of gene co-regulation in insecticide resistant house flies, Musca domestica.
abstract: BACKGROUND
  Studies suggest that not only is insecticide resistance conferred via multiple gene up-regulation, but it is mediated through the interaction of regulatory factors. However, no regulatory factors in insecticide resistance have yet been identified, and there has been no examination of the regulatory interaction of resistance genes. Our current study generated the first reference transcriptome from the adult house fly and conducted a whole transcriptome analysis for the multiple insecticide resistant strain ALHF (wild-type) and two insecticide susceptible strains: aabys (with morphological recessive markers) and CS (wild type) to gain valuable insights into the gene interaction and complex regulation in insecticide resistance of house flies, Musca domestica.
  
  
  RESULTS
  Over 56 million reads were used to assemble the adult female M. domestica transcriptome reference and 14488 contigs were generated from the de novo transcriptome assembly. A total of 6159 (43%) of the contigs contained coding regions, among which 1316 genes were identified as being co-up-regulated in ALHF in comparison to both aabys and CS. The majority of these up-regulated genes fell within the SCOP categories of metabolism, general, intra-cellular processes, and regulation, and covered three key detailed function categories: redox detailed function category in metabolism, signal transduction and kinases/phosphatases in regulation, and proteases in intra-cellular processes. The redox group contained detoxification gene superfamilies, including cytochrome P450s, glutathione S-transferases, and esterases. The signal transduction and kinases/phosphatases groups contained gene families of rhodopsin-like GPCRs, adenylate and guanylate cyclases, protein kinases and phosphatases. The proteases group contained genes with digestive, catalytic, and proteinase activities. Genetic linkage analysis with house fly lines comparing different autosomal combinations from ALHF revealed that the up-regulation of gene expression in the three key SCOP detailed function categories occurred mainly through the co-regulation of factors among multiple autosomes, especially between autosomes 2 and 5, suggesting that signaling transduction cascades controlled by GPCRs, protein kinase/phosphates and proteases may be involved in the regulation of resistance P450 gene regulation.
  
  
  CONCLUSIONS
  Taken together, our findings suggested that not only is insecticide resistance conferred via multi-resistance mechanisms or up-regulated genes, but it is mediated through the trans and/or cis co-regulations of resistance genes.
authors.forename: Ming
authors.initials: M
authors.lastname: Li
authors.forename: William R
authors.initials: WR
authors.lastname: Reid
authors.forename: Lee
authors.initials: L
authors.lastname: Zhang
authors.forename: Jeffery G
authors.initials: JG
authors.lastname: Scott
authors.forename: Xiwu
authors.initials: X
authors.lastname: Gao
authors.forename: Michael
authors.initials: M
authors.lastname: Kristensen
authors.affiliation: Department of Entomology and Plant Pathology, Auburn University, 301 Funchess Hall, Auburn, AL 36849, USA. liunann@auburn.edu.
authors.forename: Nannan
authors.initials: N
authors.lastname: Liu
mesh_terms: D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis; D004950:Esterases / Q000096:biosynthesis; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects*; D008040:Genetic Linkage; D005982:Glutathione Transferase / Q000096:biosynthesis; D006793:Houseflies / Q000187:drug effects* / Q000235:genetics; D008658:Inactivation, Metabolic; D007305:Insecticide Resistance / Q000235:genetics*; D007306:Insecticides / Q000494:pharmacology*
chemical_list: D007306:Insecticides; D003577:Cytochrome P-450 Enzyme System; D005982:Glutathione Transferase; D004950:Esterases