Háskóli ÍslandsUniversity of IcelandLudwig, Michael ZPalsson, ArnarAlekseeva, ElenaBergman, Casey MNathan, JanakiKreitman, Martin2017-03-302017-03-302005-03-15Ludwig MZ, Palsson A, Alekseeva E, Bergman CM, Nathan J, Kreitman M (2005) Functional Evolution of a cis-Regulatory Module. PLoS Biol 3(4): e93. doi:10.1371/journal.pbio.00300931545-78851545-7885 (e-ISSN)https://hdl.handle.net/20.500.11815/233Lack of knowledge about how regulatory regions evolve in relation to their structure–function may limit the utility of comparative sequence analysis in deciphering cis-regulatory sequences. To address this we applied reverse genetics to carry out a functional genetic complementation analysis of a eukaryotic cis-regulatory module—the even-skipped stripe 2 enhancer—from four Drosophila species. The evolution of this enhancer is non-clock-like, with important functional differences between closely related species and functional convergence between distantly related species. Functional divergence is attributable to differences in activation levels rather than spatiotemporal control of gene expression. Our findings have implications for understanding enhancer structure–function, mechanisms of speciation and computational identification of regulatory modules.e93eninfo:eu-repo/semantics/openAccessBiochemistryGenetics and Molecular BiologyAgricultural and Biological SciencesEvolutionLífefnafræðiErfðafræðiSameindalíffræðiÞróun lífsinsinfo:eu-repo/semantics/articlePlos Biology10.1371/journal.pbio.0030093