PUBLICATION

Evolution of lineage-specific functions in ancient cis-regulatory modules

Authors
Pauls, S., Goode, D.K., Petrone, L., Oliveri, P., Elgar, G.
ID
ZDB-PUB-151106-7
Date
2015
Source
Open Biology   5(11): (Journal)
Registered Authors
Elgar, Greg, Goode, Debbie, Pauls, Stefan
Keywords
Sox21, cis-regulatory module, conserved non-coding element, enhancer evolution, zebrafish
MeSH Terms
  • Animals
  • Base Sequence
  • Chickens
  • Conserved Sequence*
  • Evolution, Molecular*
  • Humans
  • Molecular Sequence Data
  • Nucleotide Motifs
  • Regulatory Sequences, Nucleic Acid*
  • SOXB2 Transcription Factors/genetics
  • SOXB2 Transcription Factors/metabolism
  • Takifugu
  • Xenopus
  • Zebrafish
PubMed
26538567 Full text @ Open Biol.
Abstract
Morphological evolution is driven both by coding sequence variation and by changes in regulatory sequences. However, how cis-regulatory modules (CRMs) evolve to generate entirely novel expression domains is largely unknown. Here, we reconstruct the evolutionary history of a lens enhancer located within a CRM that not only predates the lens, a vertebrate innovation, but bilaterian animals in general. Alignments of orthologous sequences from different deuterostomes sub-divide the CRM into a deeply conserved core and a more divergent flanking region. We demonstrate that all deuterostome flanking regions, including invertebrate sequences, activate gene expression in the zebrafish lens through the same ancient cluster of activator sites. However, levels of gene expression vary between species due to the presence of repressor motifs in flanking region and core. These repressor motifs are responsible for the relatively weak enhancer activity of tetrapod flanking regions. Ray-finned fish, however, have gained two additional lineage-specific activator motifs which in combination with the ancient cluster of activators and the core constitute a potent lens enhancer. The exploitation and modification of existing regulatory potential in flanking regions but not in the highly conserved core might represent a more general model for the emergence of novel regulatory functions in complex CRMs.
Genes / Markers
Figures
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Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping