title: Genomic regions with distinct genomic distance conservation in vertebrate genomes.
abstract: BACKGROUND
  A number of vertebrate highly conserved elements (HCEs) have been detected and their genomic interval distances have been reported to be more conserved than protein coding genes among mammalian genomes. A characteristic of the human - non-mammalian comparisons is a bimodal distribution of relative distance difference of conserved consecutive HCE pairs; and it is difficult to attribute such profile to a random assortment. We therefore undertook an analysis of the human genomic regions confined by consecutive HCE pairs common to eight genomes (human, mouse, rat, chicken, frog, zebrafish, tetradon and fugu).
  
  
  RESULTS
  Among HCE pairs, we found that some consistently preserve highly conserved interval distance among genomes while others have relatively low distance conservation. Using a partition method, we detected two groups of inter-HCE regions (IHRs) with distinct distance conservation pattern in vertebrate genomes: IHR1s that are bordered by HCE pairs with relative small distance variation, and IHR2s with larger distance difference values. Compared to random background, annotated repeat sequences are significantly less frequent in IHR1s than IHR2s, which reflects a correlation between repeat sequences and the length expansion of IHRs. Both groups of IHRs are unexpectedly enriched in human indel (i.e. insertion and deletion) polymorphism-variations than random background. The correlation between the percentage of conserved sequence and human IHR length was stronger for IHR1 than IHR2. Both groups of IHRs are significantly enriched for CpG islands.
  
  
  CONCLUSIONS
  The data suggest that subsets of HCE pairs may undergo different evolutionary paths in light of their genomic distance conservation, and that sets of genomic regions pertain to HCEs, as well as the region in which HCEs reside, should be treated as integrated domains.
authors.affiliation: Key Laboratory of Systems Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, PR China. sunhong@scbit.org
authors.forename: Hong
authors.initials: H
authors.lastname: Sun
authors.forename: Geir
authors.initials: G
authors.lastname: Skogerbø
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Zheng
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.forename: Yixue
authors.initials: Y
authors.lastname: Li