The success of transgenic mosquito vector control approaches relies on well‐targeted gene expression, requiring the identification and characterization of a diverse set of mosquito promoters and transcriptional enhancers. However, few enhancers have been characterized in Anopheles gambiae to date. Here, we employ the SCRMshaw method we previously developed to predict enhancers in the A. gambiae genome, preferentially targeting vector‐relevant tissues such as the salivary glands, midgut and nervous system. We demonstrate a high overall success rate, with at least 8 of 11 (73%) tested sequences validating as enhancers in an in vivo xenotransgenic assay. Four tested sequences drive expression in either the salivary gland or the midgut, making them directly useful for probing the biology of these infection‐relevant tissues. The success of our study suggests that computational enhancer prediction should serve as an effective means for identifying A. gambiae enhancers with activity in tissues involved in malaria propagation and transmission.
A major driving force behind the evolution of species-specific traits and novel structures is alterations in gene regulatory networks (GRNs). Comprehending evolution therefore requires an understanding of the nature of changes in GRN structure and the responsible mechanisms. Here, we review two insect pigmentation GRNs in order to examine common themes in GRN evolution and to reveal some of the challenges associated with investigating changes in GRNs across different evolutionary distances at the molecular level. The pigmentation GRN in Drosophila melanogaster and other drosophilids is a well-defined network for which studies from closely related species illuminate the different ways co-option of regulators can occur. The pigmentation GRN for butterflies of the Heliconius species group is less fully detailed but it is emerging as a useful model for exploring important questions about redundancy and modularity in cis-regulatory systems. Both GRNs serve to highlight the ways in which redeployment of trans-acting factors can lead to GRN rewiring and network co-option. To gain insight into GRN evolution, we discuss the importance of defining GRN architecture at multiple levels both within and between species and of utilizing a range of complementary approaches.
Transcriptionalcis-regulatory modules, e.g., enhancers, control the time and location of metazoan gene expression. While changes in enhancers can provide a powerful force for evolution, there is also significant deep conservation of enhancers for developmentally important genes, with function and sequence characteristics maintained over hundreds of millions of years of divergence. Not well understood, however, is how the overall regulatory composition of a locus evolves, with important outstanding questions such as how many enhancers are conserved vs. novel, and to what extent are the locations of conserved enhancers within a locus maintained? We begin here to address these questions with a comparison of the respectivesingle-minded (sim)loci in the two dipteran speciesDrosophila melanogaster(fruit fly) andAedes aegypti(mosquito).simencodes a highly conserved transcription factor that mediates development of the arthropod embryonic ventral midline. We identify twosimenhancers inA. aegyptiand demonstrate that they function equivalently in both transgenic flies and mosquitoes. OneA. aegyptienhancer is highly similar to a knownDrosophilacounterpart in its activity, location, and autoregulatory capability. The other differs from any knownDrosophila simenhancers with a novel location, failure to autoregulate, and regulation of expression in a unique subset of midline cells. Our results suggest that the conserved pattern ofsimexpression in the two species is the result of both conserved and novel regulatory sequences. Further examination of this locus will help to illuminate how the overall regulatory landscape of a conserved developmental gene evolves.AUTHOR SUMMARYThe expression patterns and roles of genes, especially those involved in core developmental processes, are often conserved over vast evolutionary distances. Paradoxically, the DNA sequences surrounding these genes, which contain thecis-regulatory sequences (enhancers) that regulate gene expression, tend to be highly diverged. The manner and extent to which enhancers are functionally conserved, and how the overall organization of regulatory sequences within a locus is preserved or restructured, is not well understood. In this paper, we investigate these questions by identifying enhancers controlling expression of a master nervous system regulatory gene namedsimin the mosquitoAedes aegypti, and comparing their functions and locations to those in the well-characterizedsimlocus of the fruit flyDrosophila melanogaster. Our results show that the two species generate identical patterns ofsimexpression through a mix of conserved and novel regulatory sequences. Continued exploration of thesimlocus in these two species will help to build a comprehensive picture of how a regulatory locus for a master developmental regulator has evolved.
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