title: Quantitative genome-wide enhancer activity maps for five Drosophila species show functional enhancer conservation and turnover during cis-regulatory evolution.
abstract: Phenotypic differences between closely related species are thought to arise primarily from changes in gene expression due to mutations in cis-regulatory sequences (enhancers). However, it has remained unclear how frequently mutations alter enhancer activity or create functional enhancers de novo. Here we use STARR-seq, a recently developed quantitative enhancer assay, to determine genome-wide enhancer activity profiles for five Drosophila species in the constant trans-regulatory environment of Drosophila melanogaster S2 cells. We find that the functions of a large fraction of D. melanogaster enhancers are conserved for their orthologous sequences owing to selection and stabilizing turnover of transcription factor motifs. Moreover, hundreds of enhancers have been gained since the D. melanogaster-Drosophila yakuba split about 11 million years ago without apparent adaptive selection and can contribute to changes in gene expression in vivo. Our finding that enhancer activity is often deeply conserved and frequently gained provides functional insights into regulatory evolution.
authors.affiliation: 1] Research Institute of Molecular Pathology (IMP), Vienna Biocenter (VBC), Vienna, Austria. [2].
authors.forename: Cosmas D
authors.initials: CD
authors.lastname: Arnold
authors.affiliation: 1] Research Institute of Molecular Pathology (IMP), Vienna Biocenter (VBC), Vienna, Austria. [2] [3].
authors.forename: Daniel
authors.initials: D
authors.lastname: Gerlach
authors.affiliation: Research Institute of Molecular Pathology (IMP), Vienna Biocenter (VBC), Vienna, Austria.
authors.forename: Daniel
authors.initials: D
authors.lastname: Spies
authors.affiliation: 1] Department of Biology, Brandeis University, Waltham, Massachusetts, USA. [2] Rosenstiel Basic Medical Science Research Center at Brandeis University, Waltham, Massachusetts, USA. [3].
authors.forename: Jessica A
authors.initials: JA
authors.lastname: Matts
authors.affiliation: 1] Department of Biology, Brandeis University, Waltham, Massachusetts, USA. [2] Rosenstiel Basic Medical Science Research Center at Brandeis University, Waltham, Massachusetts, USA.
authors.forename: Yuliya A
authors.initials: YA
authors.lastname: Sytnikova
authors.affiliation: Research Institute of Molecular Pathology (IMP), Vienna Biocenter (VBC), Vienna, Austria.
authors.forename: Michaela
authors.initials: M
authors.lastname: Pagani
authors.affiliation: 1] Department of Biology, Brandeis University, Waltham, Massachusetts, USA. [2] Rosenstiel Basic Medical Science Research Center at Brandeis University, Waltham, Massachusetts, USA.
authors.forename: Nelson C
authors.initials: NC
authors.lastname: Lau
authors.affiliation: Research Institute of Molecular Pathology (IMP), Vienna Biocenter (VBC), Vienna, Austria.
authors.forename: Alexander
authors.initials: A
authors.lastname: Stark
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D004330:Drosophila / Q000145:classification / Q000235:genetics* / Q000254:growth & development; D029721:Drosophila Proteins / Q000235:genetics*; D004742:Enhancer Elements, Genetic / Q000235:genetics*; D019143:Evolution, Molecular; D020869:Gene Expression Profiling; D016678:Genome; D059014:High-Throughput Nucleotide Sequencing; D008156:Luciferases / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D029721:Drosophila Proteins; D014157:Transcription Factors; D008156:Luciferases