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  REforge Associates Transcription Factor Binding Site Divergence in Regulatory Elements with Phenotypic Differences between Species.

Langer, B., Roscito, J., & Hiller, M. (2018). REforge Associates Transcription Factor Binding Site Divergence in Regulatory Elements with Phenotypic Differences between Species. Molecular biology and evolution, 35(12), 3027-3040. doi:10.1093/molbev/msy187.

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 Creators:
Langer, Björn1, Author           
Roscito, Juliana1, Author           
Hiller, Michael1, Author           
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1Max Planck Institute for Molecular Cell Biology and Genetics, Max Planck Society, ou_2340692              

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 Abstract: Elucidating the genomic determinants of morphological differences between species is key to understanding how morphological diversity evolved. While differences in cis-regulatory elements are an important genetic source for morphological evolution, it remains challenging to identify regulatory elements involved in phenotypic differences. Here, we present Regulatory Element forward genomics (REforge), a computational approach that detects associations between transcription factor binding site divergence in putative regulatory elements and phenotypic differences between species. By simulating regulatory element evolution in silico, we show that this approach has substantial power to detect such associations. To validate REforge on real data, we used known binding motifs for eye-related transcription factors and identified significant binding site divergence in vision-impaired subterranean mammals in 1% of all conserved noncoding elements. We show that these genomic regions are significantly enriched in regulatory elements that are specifically active in mouse eye tissues, and that several of them are located near genes, which are required for eye development and photoreceptor function and are implicated in human eye disorders. Thus, our genome-wide screen detects widespread divergence of eye-regulatory elements and highlights regulatory regions that likely contributed to eye degeneration in subterranean mammals. REforge has broad applicability to detect regulatory elements that could be involved in many other phenotypes, which will help to reveal the genomic basis of morphological diversity.

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 Dates: 2018-12-01
 Publication Status: Issued
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 Identifiers: DOI: 10.1093/molbev/msy187
Other: cbg-7220
PMID: 30256993
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Title: Molecular biology and evolution
  Other : Mol Biol Evol
Source Genre: Journal
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Pages: - Volume / Issue: 35 (12) Sequence Number: - Start / End Page: 3027 - 3040 Identifier: -