title: Redeployment of a conserved gene regulatory network during Aedes aegypti development.
abstract: Changes in gene regulatory networks (GRNs) underlie the evolution of morphological novelty and developmental system drift. The fruitfly Drosophila melanogaster and the dengue and Zika vector mosquito Aedes aegypti have substantially similar nervous system morphology. Nevertheless, they show significant divergence in a set of genes co-expressed in the midline of the Drosophila central nervous system, including the master regulator single minded and downstream genes including short gastrulation, Star, and NetrinA. In contrast to Drosophila, we find that midline expression of these genes is either absent or severely diminished in A. aegypti. Instead, they are co-expressed in the lateral nervous system. This suggests that in A. aegypti this "midline GRN" has been redeployed to a new location while lost from its previous site of activity. In order to characterize the relevant GRNs, we employed the SCRMshaw method we previously developed to identify transcriptional cis-regulatory modules in both species. Analysis of these regulatory sequences in transgenic Drosophila suggests that the altered gene expression observed in A. aegypti is the result of trans-dependent redeployment of the GRN, potentially stemming from cis-mediated changes in the expression of sim and other as-yet unidentified regulators. Our results illustrate a novel "repeal, replace, and redeploy" mode of evolution in which a conserved GRN acquires a different function at a new site while its original function is co-opted by a different GRN. This represents a striking example of developmental system drift in which the dramatic shift in gene expression does not result in gross morphological changes, but in more subtle differences in development and function of the late embryonic nervous system.
authors.affiliation: Department of Biochemistry, University at Buffalo-State University of New York, Buffalo, NY, United States; NY State Center of Excellence in Bioinformatics and Life Sciences, Buffalo, NY, United States.
authors.forename: Kushal
authors.initials: K
authors.lastname: Suryamohan
authors.affiliation: Department of Computer Science, University of Illinois Urbana-Champaign, Champaign, IL, United States.
authors.forename: Casey
authors.initials: C
authors.lastname: Hanson
authors.affiliation: Indiana University School of Medicine, Department of Medical and Molecular Genetics, South Bend, IN, United States.
authors.forename: Emily
authors.initials: E
authors.lastname: Andrews
authors.affiliation: Department of Computer Science, University of Illinois Urbana-Champaign, Champaign, IL, United States.
authors.forename: Saurabh
authors.initials: S
authors.lastname: Sinha
authors.affiliation: Indiana University School of Medicine, Department of Medical and Molecular Genetics, South Bend, IN, United States; University of Notre Dame, Eck Inst. for Global Health and Department of Biological Sciences, South Bend, IN, United States.
authors.forename: Molly Duman
authors.initials: MD
authors.lastname: Scheel
authors.affiliation: Department of Biochemistry, University at Buffalo-State University of New York, Buffalo, NY, United States; NY State Center of Excellence in Bioinformatics and Life Sciences, Buffalo, NY, United States; Department of Biological Sciences and Department of Biomedical Informatics, University at Buffalo-State University of New York, Buffalo, NY, United States; Department of Molecular and Cellular Biology and Program in Cancer Genetics, Roswell Park Cancer Institute, Buffalo, NY, United States. Electronic address: mshalfon@buffalo.edu.
authors.forename: Marc S
authors.initials: MS
authors.lastname: Halfon
mesh_terms: D000330:Aedes / Q000196:embryology / Q000235:genetics*; D000818:Animals; D030801:Animals, Genetically Modified; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000502:physiology; D019521:Body Patterning / Q000235:genetics; D017124:Conserved Sequence; D003465:Culex / Q000196:embryology / Q000235:genetics; D029721:Drosophila Proteins / Q000235:genetics / Q000502:physiology; D004331:Drosophila melanogaster / Q000196:embryology / Q000235:genetics; D019143:Evolution, Molecular; D018507:Gene Expression Regulation, Developmental; D053263:Gene Regulatory Networks / Q000235:genetics; D017344:Genes, Insect; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000502:physiology; D009420:Nervous System / Q000196:embryology*; D055495:Neurogenesis / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics / Q000502:physiology; D013045:Species Specificity
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D029721:Drosophila Proteins; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; C089449:sim protein, Drosophila
keywords: Aedes aegypti; Central Nervous System (CNS) development; Developmental system drift; Drosophila melanogaster; Enhancer discovery; Evolution of regulatory networks; GRN; Gene regulatory networks; Neofunctionalization; Ventral midline; Zika vector mosquito