E-GEOD-48251 - Quantitative genome-wide enhancer activity maps for five Drosophila species show functional enhancer conservation and turnover during cis-regulatory evolution
Released on 28 April 2014, last updated on 31 May 2014
Drosophila ananassae, Drosophila melanogaster, Drosophila pseudoobscura, Drosophila willistoni, Drosophila yakuba
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 D. melanogaster S2 cells. We find that the function of a large fraction of D. melanogaster enhancers is conserved in their orthologous sequences due to selection and stabilizing turnover of transcription factor motifs. Moreover, hundreds of enhancers have been gained since the D. melanogaster – D. yakuba split about 11 million years ago without apparent adaptive selection and can contribute to gene expression changes in vivo. Our finding that enhancer activity is often deeply conserved and frequently gained provides important functional insights into regulatory evolution. STARR-seq was performed in S2 cells with paired-end sequencing in two replicates and respective inputs using genomic DNA from different Drosophila species. RNA-seq was performed in a non-stranded manner without replicates for two Drosophila species.
RNA-seq of coding RNA, RNA-seq of non coding RNA
Daniel Gerlach <email@example.com>, Alexander Stark, Cosmas D Arnold, Daniel Spies, Jessica A Matts, Michaela Pagani, Nelson C Lau, Yuliya A Sytnikova