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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.

journal_name

Nat Genet

journal_title

Nature genetics

authors

Arnold CD,Gerlach D,Spies D,Matts JA,Sytnikova YA,Pagani M,Lau NC,Stark A

doi

10.1038/ng.3009

subject

Has Abstract

pub_date

2014-07-01 00:00:00

pages

685-92

issue

7

eissn

1061-4036

issn

1546-1718

pii

ng.3009

journal_volume

46

pub_type

杂志文章

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