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The nuclear OXPHOS genes in insecta: a common evolutionary origin, a common cis-regulatory motif, a common destiny for gene duplicates

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BMC EVOLUTIONARY BIOLOGY 2007年第1期7卷 215-215页

作者： Porcelli, Damiano Barsanti, Paolo Pesole, Graziano Caggese, Corrado Univ Bari Dipartimento Genet & Microbiol I-70121 Bari Italy Univ Bari Dipartimento Biochim I-70121 Bari Italy

Background: When orthologous sequences from species distributed throughout an optimal range of divergence times are available, comparative genomics is a powerful tool to address problems such as the identification of the forces that shape gene structure during evolution, although the functional constraints involved may vary in different genes and lineages. Results: We identified and annotated in the MitoComp2 dataset the orthologs of 68 nuclear genes controlling oxidative phosphorylation in 11 Drosophilidae species and in five non-Drosophilidae insects, and compared them with each other and with their counterparts in three vertebrates (Fugu rubripes, Danio rerio and Homo sapiens) and in the cnidarian Nematostella vectensis, taking into account conservation of gene structure and regulatory motifs, and preservation of gene paralogs in the genome. Comparative analysis indicates that the ancestral insect OXPHOS genes were intron rich and that extensive intron loss and lineage-specific intron gain occurred during evolution. Comparison with vertebrates and cnidarians also shows that many OXPHOS gene introns predate the cnidarian/ Bilateria evolutionary split. The nuclear respiratory gene element (NRG) has played a key role in the evolution of the insect OXPHOS genes;it is constantly conserved in the OXPHOS orthologs of all the insect species examined, while their duplicates either completely lack the element or possess only relics of the motif. Conclusion: Our observations reinforce the notion that the common ancestor of most animal phyla had intron-rich gene, and suggest that changes in the pattern of expression of the gene facilitate the fixation of duplications in the genome and the development of novel genetic functions.

关键词： Insect Species Fugu Intron Position noncoding sequence Intron Loss

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TFCONES: A database of vertebrate transcription factor-encoding genes and their associated conserved noncoding elements

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BMC GENOMICS 2007年第1期8卷 441-441页

作者： Lee, Alison P. Yang, Yuchen Brenner, Sydney Venkatesh, Byrappa Natl Univ Singapore Inst Mol & Cell Biol Singapore 138673 Singapore

Background: Transcription factors (TFs) regulate gene transcription and play pivotal roles in various biological processes such as development, cell cycle progression, cell differentiation and tumor suppression. Identifying cis-regulatory elements associated with TF-encoding genes is a crucial step in understanding gene regulatory networks. To this end, we have used a comparative genomics approach to identify putative cis-regulatory elements associated with TF-encoding genes in vertebrates. Description: We have created a database named TFCONES ( Transcription Factor Genes & Associated COnserved noncoding ElementS) ( http://***) which contains all human, mouse and fugu TF-encoding genes and conserved noncoding elements (CNEs) associated with them. The CNEs were identified by gene-by-gene alignments of orthologous TF-encoding gene loci using MLAGAN. We also predicted putative transcription factor binding sites within the CNEs. A significant proportion of human-fugu CNEs contain experimentally defined binding sites for transcriptional activators and repressors, indicating that a majority of the CNEs may function as transcriptional regulatory elements. The TF-encoding genes that are involved in nervous system development are generally enriched for human-fugu CNEs. Users can retrieve TF-encoding genes and their associated CNEs by conducting a keyword search or by selecting a family of DNA-binding proteins. Conclusion: The conserved noncoding elements identified in TFCONES represent a catalog of highly prioritized putative cis-regulatory elements of TF-encoding genes and are candidates for functional assay.

关键词： Additional Data File Fugu noncoding sequence Transcriptional Regulatory Element Nserved

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Mining the HapMap to dissect complex traits

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Genome biology 2006年第3期7卷 310页

作者： Sung K Kim Justin Borevitz Molecular and Computational Biology Program Department of Biological Sciences University of Southern California Los Angeles CA 90089 USA. sungkkim@usc.edu

A report on the Keystone Symposium 'Genome sequence Variation and the Inherited Basis of Common Disease and Complex Traits', Big Sky, USA, 8-13 January 2006.

关键词： Complex Trait noncoding sequence HapMap Data Deletion Polymorphism Fred Hutchinson Cancer Research

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Selective constraint on noncoding regions of hominid genomes

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PLOS COMPUTATIONAL BIOLOGY 2005年第7期1卷 593-598页

作者： Bush, Eliot C. Lahn, Bruce T. Univ Chicago Howard Hughes Med Inst Dept Human Genet Chicago IL 60637 USA

An important challenge for human evolutionary biology is to understand the genetic basis of human-chimpanzee differences. One influential idea holds that such differences depend, to a large extent, on adaptive changes in gene expression. An important step in assessing this hypothesis involves gaining a better understanding of selective constraint on noncoding regions of hominid genomes. In noncoding sequence, functional elements are frequently small and can be separated by large nonfunctional regions. For this reason, constraint in hominid genomes is likely to be patchy. Here we use conservation in more distantly related mammals and amniotes as a way of identifying small sequence windows that are likely to be functional. We find that putatively functional noncoding elements defined in this manner are subject to significant selective constraint in hominids.

关键词： .PLoS identifying functional elements windows account distantly selective constraint human–chimpanzee Regions of Hominid noncoding sequence mammals and amniotes small sequence constraint in hominids

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Large-scale discovery and validation of functional elements in the human genome

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Genome biology 2005年第3期6卷 312页

作者： Bradley E Bernstein Manolis Kellis Broad Institute of Harvard and Massachusetts Institute of Technology Cambridge MA 02139 USA. bbernst@fas.harvard.edu

A report on the genomics workshop 'Identification of Functional Elements in Mammalian Genomes', Cold Spring Harbor, New York, 11-13 November 2004.

关键词： Fugu Functional Element Motif Discovery noncoding sequence Enhance Green Fluorescent Protein Expression

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Computational prediction of transcription-factor binding site locations

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Genome Biology 2004年第1期5卷 1-11页

作者： Bulyk, Martha L. Division of Genetics Department of Medicine Brigham and Women's Hospital Boston MA 02115 77 Avenue Louis Pasteur United States

Identifying genomic locations of transcription-factor binding sites, particularly in higher eukaryotic genomes, has been an enormous challenge. Various experimental and computational approaches have been used to detec... 详细信息

关键词： Functional Element noncoding sequence Position Weight Matrix Phylogenetic Footprinting Transcriptional Enhancer

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Benchmarking tools for the alignment of functional noncoding DNA (vol 5, pg 6, 2004)

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BMC BIOINFORMATICS 2004年第1期5卷 6-6页

作者： Pollard, DA Bergman, CM Stoye, J Celniker, SE Eisen, MB Univ Calif Berkeley Biophys Grad Grp Berkeley CA 94720 USA Lawrence Orlando Berkeley Natl Lab Div Life Sci Dept Genome Sci Berkeley CA 94720 USA Lawrence Berkeley Natl Lab Berkeley Drosophila Genome Project Berkeley CA 94720 USA Univ Bielefeld Tech Fak D-33594 Bielefeld Germany Univ Calif Berkeley Dept Mol & Cell Biol Berkeley CA 94720 USA

Numerous tools have been developed to align genomic sequences. However, their relative performance in specific applications remains poorly characterized. Alignments of protein-coding sequences typically have been benchmarked against "correct" alignments inferred from structural data. For noncoding sequences, where such independent validation is lacking, simulation provides an effective means to generate "correct" alignments with which to benchmark alignment tools. Results Using rates of noncoding sequence evolution estimated from the genus Drosophila, we simulated alignments over a range of divergence times under varying models incorporating point substitution, insertion/deletion events, and short blocks of constrained sequences such as those found in cis-regulatory regions. We then compared "correct" alignments generated by a modified version of the ROSE simulation platform to alignments of the simulated derived sequences produced by eight pairwise alignment tools (Avid, BlastZ, Chaos, ClustalW, DiAlign, Lagan, Needle, and WABA) to determine the off-the-shelf performance of each tool. As expected, the ability to align noncoding sequences accurately decreases with increasing divergence for all tools, and declines faster in the presence of insertion/deletion evolution. Global alignment tools (Avid, ClustalW, Lagan, and Needle) typically have higher sensitivity over entire noncoding sequences as well as in constrained sequences. Local tools (BlastZ, Chaos, and WABA) have lower overall sensitivity as a consequence of incomplete coverage, but have high specificity to detect constrained sequences as well as high sensitivity within the subset of sequences they align. Tools such as DiAlign, which generate both local and global outputs, produce alignments of constrained sequences with both high sensitivity and specificity for divergence distances in the range of 1.25-3.0 substitutions per site. Conclusion For species with genomic properties similar to Drosophila, we conclud

关键词： noncoding Region Maximal Chain Constraint Specificity noncoding sequence Constraint Coverage

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Chimp genome released

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Genome Biology 2003年第1期4卷 1-3页

作者： Russo, Eugene

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Conservation of regulatory elements between two species of Drosophila

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BMC BIOINFORMATICS 2003年第1期4卷 57-57页

作者： Emberly, E Rajewsky, N Siggia, ED Rockefeller Univ Ctr Studies Phys & Biol New York NY 10021 USA NYU Dept Biol New York NY 10003 USA

Background: One of the important goals in the post-genomic era is to determine the regulatory elements within the non-coding DNA of a given organism's genome. The identification of functional cis-regulatory modules has proven difficult since the component factor binding sites are small and the rules governing their arrangement are poorly understood. However, the genomes of suitably diverged species help to predict regulatory elements based on the generally accepted assumption that conserved blocks of genomic sequence are likely to be functional. To judge the efficacy of strategies that prefilter by sequence conservation it is important to know to what extent the converse assumption holds, namely that functional elements common to both species will fall within these conserved blocks. The recently completed sequence of a second Drosophila species provides an opportunity to test this assumption for one of the experimentally best studied regulatory networks in multicellular organisms, the body patterning of the fly embryo. Results: We find that 50%-70% of known binding sites reside in conserved sequence blocks, but these percentages are not greatly enriched over what is expected by chance. Finally, a computational genome-wide search in both species for regulatory modules based on clusters of binding sites suggests that genes central to the regulatory network are consistently recovered. Conclusions: Our results indicate that binding sites remain clustered for these "core modules" while not necessarily residing in conserved blocks. This is an important clue as to how regulatory information is encoded in the genome and how modules evolve.

关键词： Module Prediction Alignment Program noncoding sequence Body Patterning Interspecies Comparison

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Multi-species sequence comparison: the next frontier in genome annotation

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GENOME BIOLOGY 2003年第12期4卷 122-122页

作者： Dubchak, I Frazer, K Univ Calif Berkeley Lawrence Berkeley Lab Genom Div Berkeley CA 94720 USA Perlegen Sci Mountain View CA 94043 USA

Multi-species comparisons of DNA sequences are more powerful for discovering functional sequences than pairwise DNA sequence comparisons. Most current computational tools have been designed for pairwise comparisons, and efficient extension of these tools to multiple species will require knowledge of the ideal evolutionary distance to choose and the development of new algorithms for alignment, analysis of conservation, and visualization of results.

关键词： Multiple Alignment Pairwise Alignment Global Alignment Stem Cell Leukemia noncoding sequence

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