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      Ultraconserved coding regions outside the homeobox of mammalian Hox genes

      research-article
      1 , 2 , , 1 , 2 , 1 , 2
      BMC Evolutionary Biology
      BioMed Central

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          Abstract

          Background

          All bilaterian animals share a general genetic framework that controls the formation of their body structures, although their forms are highly diversified. The Hox genes that encode transcription factors play a central role in this framework. All Hox proteins contain a highly conserved homeodomain encoded by the homeobox motif, but the other regions are generally assumed to be less conserved. In this study, we used comparative genomic methods to infer possible functional elements in the coding regions of mammalian Hox genes.

          Results

          We identified a set of ultraconserved coding regions (UCRs) outside the homeobox of mammalian Hox genes. Here a UCR is defined as a region of at least 120 nucleotides without synonymous and nonsynonymous nucleotide substitutions among different orders of mammals. Further analysis has indicated that these UCRs occur only in placental mammals and they evolved apparently after the split of placental mammals from marsupials. Analysis of human SNP data suggests that these UCRs are maintained by strong purifying selection.

          Conclusion

          Although mammalian genomes are known to contain ultraconserved non-coding elements (UNEs), this paper seems to be the first to report the UCRs in protein coding genes. The extremely high degree of sequence conservation in non-homeobox regions suggests that they might have important roles for the functions of Hox genes. We speculate that UCRs have some gene regulatory functions possibly in relation to the development of the intra-uterus child-bearing system.

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          Most cited references38

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          TimeTree: a public knowledge-base of divergence times among organisms.

          Biologists and other scientists routinely need to know times of divergence between species and to construct phylogenies calibrated to time (timetrees). Published studies reporting time estimates from molecular data have been increasing rapidly, but the data have been largely inaccessible to the greater community of scientists because of their complexity. TimeTree brings these data together in a consistent format and uses a hierarchical structure, corresponding to the tree of life, to maximize their utility. Results are presented and summarized, allowing users to quickly determine the range and robustness of time estimates and the degree of consensus from the published literature. TimeTree is available at http://www.timetree.net
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            Predictive identification of exonic splicing enhancers in human genes.

            Specific short oligonucleotide sequences that enhance pre-mRNA splicing when present in exons, termed exonic splicing enhancers (ESEs), play important roles in constitutive and alternative splicing. A computational method, RESCUE-ESE, was developed that predicts which sequences have ESE activity by statistical analysis of exon-intron and splice site composition. When large data sets of human gene sequences were used, this method identified 10 predicted ESE motifs. Representatives of all 10 motifs were found to display enhancer activity in vivo, whereas point mutants of these sequences exhibited sharply reduced activity. The motifs identified enable prediction of the splicing phenotypes of exonic mutations in human genes.
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              Synonymous codon usage in Drosophila melanogaster: natural selection and translational accuracy.

              H Akashi (1994)
              I present evidence that natural selection biases synonymous codon usage to enhance the accuracy of protein synthesis in Drosophila melanogaster. Since the fitness cost of a translational misincorporation will depend on how the amino acid substitution affects protein function, selection for translational accuracy predicts an association between codon usage in DNA and functional constraint at the protein level. The frequency of preferred codons is significantly higher at codons conserved for amino acids than at nonconserved codons in 38 genes compared between D. melanogaster and Drosophila virilis or Drosophila pseudoobscura (Z = 5.93, P < 10(-6)). Preferred codon usage is also significantly higher in putative zinc-finger and homeodomain regions than in the rest of 28 D. melanogaster transcription factor encoding genes (Z = 8.38, P < 10(-6)). Mutational alternatives (within-gene differences in mutation rates, amino acid changes altering codon preference states, and doublet mutations at adjacent bases) do not appear to explain this association between synonymous codon usage and amino acid constraint.
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                Author and article information

                Journal
                BMC Evol Biol
                BMC Evolutionary Biology
                BioMed Central
                1471-2148
                2008
                24 September 2008
                : 8
                : 260
                Affiliations
                [1 ]Department of Biology and Institute of Molecular Evolutionary Genetics, Pennsylvania State University, University Park, PA 16802, USA
                [2 ]Huck Institutes of Life Sciences, Pennsylvania State University, University Park, PA 16802, USA
                Article
                1471-2148-8-260
                10.1186/1471-2148-8-260
                2566984
                18816392
                9c1a4cd6-8851-4c9d-8c90-79affc5f5d79
                Copyright © 2008 Lin et al; licensee BioMed Central Ltd.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 27 May 2008
                : 24 September 2008
                Categories
                Research Article

                Evolutionary Biology
                Evolutionary Biology

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