Title: Functionally conserved enhancers with divergent sequences in distant vertebrates

Abstract

© 2015 Yang et al. Background: To examine the contributions of sequence and function conservation in the evolution of enhancers, we systematically identified enhancers whose sequences are not conserved among distant groups of vertebrate species, but have homologous function and are likely to be derived from a common ancestral sequence. Our approach combined comparative genomics and epigenomics to identify potential enhancer sequences in the genomes of three groups of distantly related vertebrate species. Results: We searched for sequences that were conserved within groups of closely related species but not between groups of more distant species, and were associated with an epigenetic mark of enhancer activity. To facilitate inferring orthology between non-conserved sequences, we limited our search to introns whose orthology could be unambiguously established by mapping the bracketing exons. We show that a subset of these non-conserved but syntenic sequences from the mouse and zebrafish genomes have homologous functions in a zebrafish transgenic enhancer assay. The conserved expression patterns driven by these enhancers are probably associated with short transcription factor-binding motifs present in the divergent sequences. Conclusions: We have identified numerous potential enhancers with divergent sequences but a conserved function. These results indicate that selection on function, rather than sequence,more » may be a common mode of enhancer evolution; evidence for selection at the sequence level is not a necessary criterion to define a gene regulatory element.« less

Authors:

Yang, Song; Oksenberg, Nir; Takayama, Sachiko; Heo, Seok-Jin; Poliakov, Alexander; Ahituv, Nadav; Dubchak, Inna; Boffelli, Dario

Publication Date:

Fri Oct 30 00:00:00 EDT 2015

Research Org.:

Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)

Sponsoring Org.:

USDOE Office of Science (SC)

OSTI Identifier:

1618538

Alternate Identifier(s):

OSTI ID: 1256483; OSTI ID: 1378614

Grant/Contract Number:  

AC02-05CH11231; HL091495; R01HG005058; 1R01HG006768; R01HD059862; GM61390; 1R01DK090382; 1R01NS079231

Resource Type:

Published Article

Journal Name:

BMC Genomics

Additional Journal Information:

Journal Name: BMC Genomics Journal Volume: 16 Journal Issue: 1; Journal ID: ISSN 1471-2164

Publisher:

Springer Science + Business Media

Country of Publication:

United Kingdom

Language:

English

Subject:

59 BASIC BIOLOGICAL SCIENCES