ArticleDevelopment (Cambridge, England)2011
Minor change, major difference: divergent functions of highly conserved cis-regulatory elements subsequent to whole genome duplication events.
Article in Development (Cambridge, England), 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
19 citing papers in PubMed.
- Identification and characterization of Hand2 upstream genomic enhancers active in developing stomach and limbs.Developmental dynamics : an official publication of the American Association of Anatomists · 2024Article
- A novel conserved enhancer at zebrafish zic3 and zic6 loci drives neural expression.Developmental dynamics : an official publication of the American Association of Anatomists · 2019Article
- Chromatin Evolution-Key Innovations Underpinning Morphological Complexity.Frontiers in plant science · 2019Review
- Functional Conservation of a Developmental Switch in Mammals since the Jurassic Age.Molecular biology and evolution · 2019Article
- Differential Gene Expression in the Human Brain Is Associated with Conserved, but Not Accelerated, Noncoding Sequences.Molecular biology and evolution · 2017Article
- Comparative analyses of super-enhancers reveal conserved elements in vertebrate genomes.Genome research · 2017Article
- Review
- A de novo silencer causes elimination of MITF-M expression and profound hearing loss in pigs.BMC biology · 2016Article
- Functional and Comparative Genomics of Hoxa2 Gene cis-Regulatory Elements: Evidence for Evolutionary Modification of Ancestral Core Element Activity.Journal of developmental biology · 2016Article
- A reporter assay in lamprey embryos reveals both functional conservation and elaboration of vertebrate enhancers.PloS one · 2014Article
- Evolution of transcriptional enhancers and animal diversity.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2013Article
- Extensive conservation of ancient microsynteny across metazoans due to cis-regulatory constraints.Genome research · 2012Article
- Evolution of a tissue-specific silencer underlies divergence in the expression of pax2 and pax8 paralogues.Nature communications · 2012Article
- Regulatory genomics: Insights from the zebrafish.Current topics in genetics · 2012Article
- Article
- Conserved and non-conserved enhancers direct tissue specific transcription in ancient germ layer specific developmental control genes.BMC developmental biology · 2011Article
- Fishing for function: zebrafish BAC transgenics for functional genomics.Molecular bioSystems · 2011Review
- Dissecting the transcriptional regulatory properties of human chromosome 16 highly conserved non-coding regions.PloS one · 2011Article
- Functional analysis of conserved non-coding regions around the short stature hox gene (shox) in whole zebrafish embryos.PloS one · 2011Article
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Authors and funding
5 authors.
Funding
Abstract
Within the vertebrate lineage, a high proportion of duplicate genes have been retained after whole genome duplication (WGD) events. It has been proposed that many of these duplicate genes became indispensable because the ancestral gene function was divided between them. In addition, novel functions may have evolved, owing to changes in cis-regulatory elements. Functional analysis of the PAX2/5/8 gene subfamily appears to support at least the first part of this hypothesis. The collective role of these genes has been widely retained, but sub-functions have been differentially partitioned between the genes in different vertebrates. Conserved non-coding elements (CNEs) represent an interesting and readily identifiable class of putative cis-regulatory elements that have been conserved from fish to mammals, an evolutionary distance of 450 million years. Within the PAX2/5/8 gene subfamily, PAX2 is associated with the highest number of CNEs. An additional WGD experienced in the teleost lineage led to two copies of pax2, each of which retained a large proportion of these CNEs. Using a reporter gene assay in zebrafish embryos, we have exploited this rich collection of regulatory elements in order to determine whether duplicate CNEs have evolved different functions. Remarkably, we find that even highly conserved sequences exhibit more functional differences than similarities. We also discover that short flanking sequences can have a profound impact on CNE function. Therefore, if CNEs are to be used as candidate enhancers for transgenic studies or for multi-species comparative analyses, it is paramount that the CNEs are accurately delineated.
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