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Identification of a conserved sequence in the non-coding regions of many human genes. 总被引:4,自引:3,他引:1
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We have analyzed a sequence of approximately 70 base pairs (bp) that shows a high degree of similarity to sequences present in the non-coding regions of a number of human and other mammalian genes. The sequence was discovered in a fragment of human genomic DNA adjacent to an integrated hepatitis B virus genome in cells derived from human hepatocellular carcinoma tissue. When one of the viral flanking sequences was compared to nucleotide sequences in GenBank, more than thirty human genes were identified that contained a similar sequence in their non-coding regions. The sequence element was usually found once or twice in a gene, either in an intron or in the 5' or 3' flanking regions. It did not share any similarities with known short interspersed nucleotide elements (SINEs) or presently known gene regulatory elements. This element was highly conserved at the same position within the corresponding human and mouse genes for myoglobin and N-myc, indicating evolutionary conservation and possible functional importance. Preliminary DNase I footprinting data suggested that the element or its adjacent sequences may bind nuclear factors to generate specific DNase I hypersensitive sites. The size, structure, and evolutionary conservation of this sequence indicates that it is distinct from other types of short interspersed repetitive elements. It is possible that the element may have a cis-acting functional role in the genome. 相似文献
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Xianjun Dong Pavla Navratilova David Fredman ?yvind Drivenes Thomas S. Becker Boris Lenhard 《Nucleic acids research》2010,38(4):1071-1085
Using a comparative genomics approach to reconstruct the fate of genomic regulatory blocks (GRBs) and identify exonic remnants that have survived the disappearance of their host genes after whole-genome duplication (WGD) in teleosts, we discover a set of 38 candidate cis-regulatory coding exons (RCEs) with predicted target genes. These elements demonstrate evolutionary separation of overlapping protein-coding and regulatory information after WGD in teleosts. We present evidence that the corresponding mammalian exons are still under both coding and non-coding selection pressure, are more conserved than other protein coding exons in the host gene and several control sets, and share key characteristics with highly conserved non-coding elements in the same regions. Their dual function is corroborated by existing experimental data. Additionally, we show examples of human exon remnants stemming from the vertebrate 2R WGD. Our findings suggest that long-range cis-regulatory inputs for developmental genes are not limited to non-coding regions, but can also overlap the coding sequence of unrelated genes. Thus, exonic regulatory elements in GRBs might be functionally equivalent to those in non-coding regions, calling for a re-evaluation of the sequence space in which to look for long-range regulatory elements and experimentally test their activity. 相似文献
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Assaying the regulatory potential of mammalian conserved non-coding sequences in human cells
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Catia Attanasio Alexandre Reymond Richard Humbert Robert Lyle Michael S Kuehn Shane Neph Peter J Sabo Jeff Goldy Molly Weaver Andrew Haydock Kristin Lee Michael Dorschner Emmanouil T Dermitzakis Stylianos E Antonarakis John A Stamatoyannopoulos 《Genome biology》2008,9(12):R168-12
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We study the length distribution functions for the 16 possible distinct dimeric tandem repeats in DNA sequences of diverse taxonomic partitions of GenBank (known human and mouse genomes, and complete genomes of Caenorhabditis elegans and yeast). For coding DNA, we find that all 16 distribution functions are exponential. For non-coding DNA, the distribution functions for most of the dimeric repeats have surprisingly long tails, that fit a power-law function. We hypothesize that: (i) the exponential distributions of dimeric repeats in protein coding sequences indicate strong evolutionary pressure against tandem repeat expansion in coding DNA sequences; and (ii) long tails in the distributions of dimers in non-coding DNA may be a result of various mutational mechanisms. These long, non-exponential tails in the distribution of dimeric repeats in non-coding DNA are hypothesized to be due to the higher tolerance of non-coding DNA to mutations. By comparing genomes of various phylogenetic types of organisms, we find that the shapes of the distributions are not universal, but rather depend on the specific class of species and the type of a dimer. 相似文献
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Conserved synteny––the sharing of at least one orthologous gene by a pair of chromosomes from two species––can, in the strictest
sense, be viewed as sequence conservation between chromosomes of two related species, irrespective of whether coding or non-coding
sequence is examined. The recent sequencing of multiple vertebrate genomes indicates that certain chromosomal segments of
considerable size are conserved in gene order as well as underlying non-coding sequence across all vertebrates. Some of these
segments lost genes or non-coding sequence and/or underwent breakage only in teleost genomes, presumably because evolutionary
pressure acting on these regions to remain intact were relaxed after an additional round of whole genome duplication. Random
reporter insertions into zebrafish chromosomes combined with computational genome-wide analysis indicate that large chromosomal
areas of multiple genes contain long-range regulatory elements, which act on their target genes from several gene distances
away. In addition, computational breakpoint analyses suggest that recurrent evolutionary breaks are found in “fragile regions”
or “hotspots”, outside of the conserved blocks of synteny. These findings cannot be accommodated by the random breakage model
and suggest that this view of genome and chromosomal evolution requires substantial reassessment. 相似文献
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Nucleotide sequence determination of guinea-pig casein B mRNA reveals homology with bovine and rat alpha s1 caseins and conservation of the non-coding regions of the mRNA. 总被引:2,自引:0,他引:2
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Nucleotide sequence analysis of cloned guinea-pig casein B cDNA sequences has identified two casein B variants related to the bovine and rat alpha s1 caseins. Amino acid homology was largely confined to the known bovine or predicted rat phosphorylation sites and within the 'signal' precursor sequence. Comparison of the deduced nucleotide sequence of the guinea-pig and rat alpha s1 casein mRNA species showed greater sequence conservation in the non-coding than in the coding regions, suggesting a functional and possibly regulatory role for the non-coding regions of casein mRNA. The results provide insight into the evolution of the casein genes, and raise questions as to the role of conserved nucleotide sequences within the non-coding regions of mRNA species. 相似文献
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Comparative genomics and regulatory evolution: conservation and function of the Chs and Apetala3 promoters 总被引:4,自引:0,他引:4
Koch MA Weisshaar B Kroymann J Haubold B Mitchell-Olds T 《Molecular biology and evolution》2001,18(10):1882-1891
DNA sequence variations of chalcone synthase (Chs) and Apetala3 gene promoters from 22 cruciferous plant species were analyzed to identify putative conserved regulatory elements. Our comparative approach confirmed the existence of numerous conserved sequences which may act as regulatory elements in both investigated promoters. To confirm the correct identification of a well-conserved UV-light-responsive promoter region, a subset of Chs promoter fragments were tested in Arabidopsis thaliana protoplasts. All promoters displayed similar light responsivenesses, indicating the general functional relevance of the conserved regulatory element. In addition to known regulatory elements, other highly conserved regions were detected which are likely to be of functional importance. Phylogenetic trees based on DNA sequences from both promoters (gene trees) were compared with the hypothesized phylogenetic relationships (species trees) of these taxa. The data derived from both promoter sequences were congruent with the phylogenies obtained from coding regions of other nuclear genes and from chloroplast DNA sequences. This indicates that promoter sequence evolution generally is reflective of species phylogeny. Our study also demonstrates the great value of comparative genomics and phylogenetics as a basis for functional analysis of promoter action and gene regulation. 相似文献