ArticlePLoS biology2005
Highly conserved non-coding sequences are associated with vertebrate development.
Article in PLoS biology, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 482 papers.
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Who cites it
482 citing papers in PubMed.
- Genome-wide discovery ofeLife · 2026Article
- A putativebioRxiv : the preprint server for biology · 2026Article
- Characterizing highly conserved fragments in 3'UTRs via statistical and transfer learning approaches.NAR genomics and bioinformatics · 2026Article
- Positive selection on brain cis-regulatory elements in the human lineage drives changes in gene expression and susceptibility to neuropsychiatric disorders.HGG advances · 2026Article
- In Depth Characterization of the Promoter Proximal Proteome of Single Copy Locus FOXP2.Molecular & cellular proteomics : MCP · 2026Article
- Lift&Add-rapid and robust addition of new species to alignments of conserved non-coding sequences.Bioinformatics (Oxford, England) · 2026Article
- A Functionally Conserved Enhancer is Critical for PGC1A Expression and Thermogenesis in Brown Fat.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Min-frame transformation enables more sensitive viral genome alignment.bioRxiv : the preprint server for biology · 2026Article
- Functional genomics analysis of developing zebrafish and human endoderm reveals highly conservedGenome research · 2026Article
- Deep conservation of cis-regulatory elements and chromatin organization in echinoderms uncover ancestral regulatory features of animal genomes.Nature ecology & evolution · 2026Article
- Evaluating Probe Design for Phylogenomics Across Taxonomic Scales: First Steps for Applying Ultraconserved Elements in an Understudied Class (Mollusca: Polyplacophora).Molecular ecology resources · 2026Article
- Two deeply conserved non-coding sequences control PLETHORA1/2 expression and coordinate embryo and root development.Plant communications · 2025Article
- Predicted deleterious mutations reveal the genetic architecture of male reproductive success in a lekking bird.Nature ecology & evolution · 2025Article
- A single-cell rice atlas integrates multi-species data to reveal cis-regulatory evolution.Nature plants · 2025Article
- Mammalian conservation of endogenous G-quadruplex reveals their associations with complex traits.Genome biology · 2025Article
- Single-cell transcriptomics of ventral forebrain progenitors identifies Evf2 enhancer lncRNA-enhancer gene guidance through direct RNA binding and RNP recruitment domains.Nature communications · 2025Article
- Genomic insights into the convergent evolution of desert adaptation in camels and antelopes.Zoological research · 2025Article
- Evolution of cetacean-specific conserved non-coding elements suggests their role in the limb changes during secondary aquatic adaptation.BMC biology · 2025Article
- Computational analysis of congenital heart disease associated SNPs: unveiling their impact on the gene regulatory system.BMC genomics · 2025Article
- Utilizing a deep learning model based on BERT for identifying enhancers and their strength.PloS one · 2025Article
422 more citing papers are in PubMed but not listed here.
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Authors and funding
16 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In addition to protein coding sequence, the human genome contains a significant amount of regulatory DNA, the identification of which is proving somewhat recalcitrant to both in silico and functional methods. An approach that has been used with some success is comparative sequence analysis, whereby equivalent genomic regions from different organisms are compared in order to identify both similarities and differences. In general, similarities in sequence between highly divergent organisms imply functional constraint. We have used a whole-genome comparison between humans and the pufferfish, Fugu rubripes, to identify nearly 1,400 highly conserved non-coding sequences. Given the evolutionary divergence between these species, it is likely that these sequences are found in, and furthermore are essential to, all vertebrates. Most, and possibly all, of these sequences are located in and around genes that act as developmental regulators. Some of these sequences are over 90% identical across more than 500 bases, being more highly conserved than coding sequence between these two species. Despite this, we cannot find any similar sequences in invertebrate genomes. In order to begin to functionally test this set of sequences, we have used a rapid in vivo assay system using zebrafish embryos that allows tissue-specific enhancer activity to be identified. Functional data is presented for highly conserved non-coding sequences associated with four unrelated developmental regulators (SOX21, PAX6, HLXB9, and SHH), in order to demonstrate the suitability of this screen to a wide range of genes and expression patterns. Of 25 sequence elements tested around these four genes, 23 show significant enhancer activity in one or more tissues. We have identified a set of non-coding sequences that are highly conserved throughout vertebrates. They are found in clusters across the human genome, principally around genes that are implicated in the regulation of development, including many transcription factors. These highly conserved non-coding sequences are likely to form part of the genomic circuitry that uniquely defines vertebrate development.
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