Human Molecular Genetics Advance Access originally published online on August 21, 2006
Human Molecular Genetics 2006 15(19):2911-2922; doi:10.1093/hmg/ddl232
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Conserved distances between vertebrate highly conserved elements
1 Bioinformatics Laboratory and National Laboratory of Biomacromolecules, Institute of Biophysics and 2 Institute of Computing Technology, Chinese Academy of Sciences, Beijing 100101, P.R., China
* To whom correspondence should be addressed at: Bioinfomatics Laboratory, Institute of Biophysics, Chinese Academy of Sciences, Datun Road 15, Beijing 100101, P.R. China. Tel: +86 1064888546; Fax: +86 1064877837; Email: crs{at}sun5.ibp.ac.cn
Received June 1, 2006; Accepted August 11, 2006
High numbers of sequence element with very high (>95%) sequence conservation between the human and other vertebrate genomes have been reported and ascribed putative cis-regulatory functions. We have investigated the structural relationships between such elements in mammalian genomes and find that not only their sequences, but also the distances between them are significantly (P<2.2x10–16) more conserved than corresponding distances between orthologous protein-coding genes or between exons within these genes. Regions of largely conserved distance between consecutive highly conserved elements (HCE) generally overlap previously identified HCE clusters, but may be far longer (up to 20 Mb) and possibly cover close to 25% of the human genome sequence. Similar conservation of distance is found between bird (chicken) and mammalian genomes and is also discernible in comparisons between fish and mammals. The data suggest either that a substantial amount of essential (functionally active) elements with lower sequence conservation occupy the space between the HCEs or that distance itself is an important factor in transcriptional regulation or chromatin modelling.
The authors wish it to be known that, in their opinion, the first two authors should be regarded as joint First Authors.
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