期刊
NATURE GENETICS
卷 46, 期 7, 页码 685-692出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/ng.3009
关键词
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资金
- European Research Council (ERC) Starting Grant [242922]
- Austrian Science Fund (FWF) [F4303-B09]
- US National Institutes of Health [HD057298]
- Searle Scholars foundation
- Boehringer Ingelheim
- European Research Council (ERC) [242922] Funding Source: European Research Council (ERC)
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.
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