TY - JOUR T1 - Three independent determinants of protein evolutionary rate JF - J Mol EvolJ Mol EvolJ Mol Evol Y1 - 2013 A1 - Choi, S. S. A1 - Sridhar Hannenhalli KW - *Evolution, Molecular KW - *Mutation Rate KW - Animals KW - Genes/physiology KW - Genetic Fitness KW - HUMANS KW - Models, Genetic KW - Protein Biosynthesis/genetics KW - Protein Folding KW - Protein Interaction Domains and Motifs/genetics KW - Proteins/chemistry/*genetics/metabolism AB - One of the most widely accepted ideas related to the evolutionary rates of proteins is that functionally important residues or regions evolve slower than other regions, a reasonable outcome of which should be a slower evolutionary rate of the proteins with a higher density of functionally important sites. Oddly, the role of functional importance, mainly measured by essentiality, in determining evolutionary rate has been challenged in recent studies. Several variables other than protein essentiality, such as expression level, gene compactness, protein-protein interactions, etc., have been suggested to affect protein evolutionary rate. In the present review, we try to refine the concept of functional importance of a gene, and consider three factors-functional importance, expression level, and gene compactness, as independent determinants of evolutionary rate of a protein, based not only on their known correlation with evolutionary rate but also on a reasonable mechanistic model. We suggest a framework based on these mechanistic models to correctly interpret the correlations between evolutionary rates and the various variables as well as the interrelationships among the variables. VL - 76 SN - 1432-1432 (Electronic)
0022-2844 (Linking) N1 - Choi, Sun Shim
Hannenhalli, Sridhar
eng
R01GM085226/GM/NIGMS NIH HHS/
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Review
Germany
2013/02/13 06:00
J Mol Evol. 2013 Mar;76(3):98-111. doi: 10.1007/s00239-013-9543-6. Epub 2013 Feb 12. J1 - Journal of molecular evolutionJournal of molecular evolution ER - TY - JOUR T1 - The partitioned LASSO-patternsearch algorithm with application to gene expression data JF - BMC bioinformaticsBMC Bioinformatics Y1 - 2012 A1 - Shi, Weiliang A1 - Wahba, Grace A1 - Irizarry, Rafael A. A1 - Héctor Corrada Bravo A1 - Wright, Stephen J. KW - algorithms KW - Breast Neoplasms KW - Computer simulation KW - Female KW - Gene expression KW - Gene Expression Profiling KW - Genomics KW - HUMANS KW - Models, Genetic AB - BACKGROUND: In systems biology, the task of reverse engineering gene pathways from data has been limited not just by the curse of dimensionality (the interaction space is huge) but also by systematic error in the data. The gene expression barcode reduces spurious association driven by batch effects and probe effects. The binary nature of the resulting expression calls lends itself perfectly to modern regularization approaches that thrive in high-dimensional settings. RESULTS: The Partitioned LASSO-Patternsearch algorithm is proposed to identify patterns of multiple dichotomous risk factors for outcomes of interest in genomic studies. A partitioning scheme is used to identify promising patterns by solving many LASSO-Patternsearch subproblems in parallel. All variables that survive this stage proceed to an aggregation stage where the most significant patterns are identified by solving a reduced LASSO-Patternsearch problem in just these variables. This approach was applied to genetic data sets with expression levels dichotomized by gene expression bar code. Most of the genes and second-order interactions thus selected and are known to be related to the outcomes. CONCLUSIONS: We demonstrate with simulations and data analyses that the proposed method not only selects variables and patterns more accurately, but also provides smaller models with better prediction accuracy, in comparison to several alternative methodologies. VL - 13 N1 - http://www.ncbi.nlm.nih.gov/pubmed/22587526?dopt=Abstract ER - TY - JOUR T1 - SplicePort--an interactive splice-site analysis tool. JF - Nucleic Acids Res Y1 - 2007 A1 - Dogan, Rezarta Islamaj A1 - Getoor, Lise A1 - Wilbur, W John A1 - Mount, Stephen M KW - Base Sequence KW - Chromosome mapping KW - Computational Biology KW - Computer simulation KW - DNA KW - Genome KW - HUMANS KW - Internet KW - Models, Genetic KW - Molecular Sequence Data KW - Pattern Recognition, Automated KW - RNA Splice Sites KW - sequence alignment KW - Sequence Analysis, DNA KW - User-Computer Interface AB -

SplicePort is a web-based tool for splice-site analysis that allows the user to make splice-site predictions for submitted sequences. In addition, the user can also browse the rich catalog of features that underlies these predictions, and which we have found capable of providing high classification accuracy on human splice sites. Feature selection is optimized for human splice sites, but the selected features are likely to be predictive for other mammals as well. With our interactive feature browsing and visualization tool, the user can view and explore subsets of features used in splice-site prediction (either the features that account for the classification of a specific input sequence or the complete collection of features). Selected feature sets can be searched, ranked or displayed easily. The user can group features into clusters and frequency plot WebLogos can be generated for each cluster. The user can browse the identified clusters and their contributing elements, looking for new interesting signals, or can validate previously observed signals. The SplicePort web server can be accessed at http://www.cs.umd.edu/projects/SplicePort and http://www.spliceport.org.

VL - 35 CP - Web Server issue M3 - 10.1093/nar/gkm407 ER - TY - JOUR T1 - Comparison of the genome of the oral pathogen Treponema denticola with other spirochete genomes JF - Proceedings of the National Academy of Sciences of the United States of AmericaProceedings of the National Academy of Sciences of the United States of America Y1 - 2004 A1 - Seshadri, Rekha A1 - Myers, Garry S. A. A1 - Tettelin, Hervé A1 - Eisen, Jonathan A. A1 - Heidelberg, John F. A1 - Dodson, Robert J. A1 - Davidsen, Tanja M. A1 - DeBoy, Robert T. A1 - Fouts, Derrick E. A1 - Haft, Dan H. A1 - J. Selengut A1 - Ren, Qinghu A1 - Brinkac, Lauren M. A1 - Madupu, Ramana A1 - Kolonay, Jamie A1 - Durkin, A. Scott A1 - Daugherty, Sean C. A1 - Shetty, Jyoti A1 - Shvartsbeyn, Alla A1 - Gebregeorgis, Elizabeth A1 - Geer, Keita A1 - Tsegaye, Getahun A1 - Malek, Joel A1 - Ayodeji, Bola A1 - Shatsman, Sofiya A1 - McLeod, Michael P. A1 - Smajs, David A1 - Howell, Jerrilyn K. A1 - Pal, Sangita A1 - Amin, Anita A1 - Vashisth, Pankaj A1 - McNeill, Thomas Z. A1 - Xiang, Qin A1 - Sodergren, Erica A1 - Baca, Ernesto A1 - Weinstock, George M. A1 - Norris, Steven J. A1 - Fraser, Claire M. A1 - Paulsen, Ian T. KW - ATP-Binding Cassette Transporters KW - Bacterial Proteins KW - Base Sequence KW - Borrelia burgdorferi KW - Genes, Bacterial KW - Genome, Bacterial KW - Leptospira interrogans KW - Models, Genetic KW - Molecular Sequence Data KW - Mouth KW - Sequence Homology, Amino Acid KW - Treponema KW - Treponema pallidum AB - We present the complete 2,843,201-bp genome sequence of Treponema denticola (ATCC 35405) an oral spirochete associated with periodontal disease. Analysis of the T. denticola genome reveals factors mediating coaggregation, cell signaling, stress protection, and other competitive and cooperative measures, consistent with its pathogenic nature and lifestyle within the mixed-species environment of subgingival dental plaque. Comparisons with previously sequenced spirochete genomes revealed specific factors contributing to differences and similarities in spirochete physiology as well as pathogenic potential. The T. denticola genome is considerably larger in size than the genome of the related syphilis-causing spirochete Treponema pallidum. The differences in gene content appear to be attributable to a combination of three phenomena: genome reduction, lineage-specific expansions, and horizontal gene transfer. Genes lost due to reductive evolution appear to be largely involved in metabolism and transport, whereas some of the genes that have arisen due to lineage-specific expansions are implicated in various pathogenic interactions, and genes acquired via horizontal gene transfer are largely phage-related or of unknown function. VL - 101 N1 - http://www.ncbi.nlm.nih.gov/pubmed/15064399?dopt=Abstract ER - TY - JOUR T1 - Sex-lethal splicing autoregulation in vivo: interactions between SEX-LETHAL, the U1 snRNP and U2AF underlie male exon skipping. JF - Development Y1 - 2003 A1 - Nagengast, Alexis A A1 - Stitzinger, Shane M A1 - Tseng, Chin-Hsiu A1 - Mount, Stephen M A1 - Salz, Helen K KW - Alternative Splicing KW - Amino Acid Sequence KW - Animals KW - Animals, Genetically Modified KW - Drosophila melanogaster KW - Drosophila Proteins KW - Exons KW - Female KW - Gene Expression Regulation, Developmental KW - Genes, Insect KW - Homeostasis KW - Male KW - Models, Genetic KW - Molecular Sequence Data KW - Nuclear Proteins KW - Point Mutation KW - Ribonucleoprotein, U1 Small Nuclear KW - Ribonucleoproteins KW - RNA Splicing KW - RNA-Binding Proteins KW - Sequence Homology, Amino Acid KW - Sex Differentiation AB -

Alternative splicing of the Sex-lethal pre-mRNA has long served as a model example of a regulated splicing event, yet the mechanism by which the female-specific SEX-LETHAL RNA-binding protein prevents inclusion of the translation-terminating male exon is not understood. Thus far, the only general splicing factor for which there is in vivo evidence for a regulatory role in the pathway leading to male-exon skipping is sans-fille (snf), a protein component of the spliceosomal U1 and U2 snRNPs. Its role, however, has remained enigmatic because of questions about whether SNF acts as part of an intact snRNP or a free protein. We provide evidence that SEX-LETHAL interacts with SANS-FILLE in the context of the U1 snRNP, through the characterization of a point mutation that interferes with both assembly into the U1 snRNP and complex formation with SEX-LETHAL. Moreover, we find that SEX-LETHAL associates with other integral U1 snRNP components, and we provide genetic evidence to support the biological relevance of these physical interactions. Similar genetic and biochemical approaches also link SEX-LETHAL with the heterodimeric splicing factor, U2AF. These studies point specifically to a mechanism by which SEX-LETHAL represses splicing by interacting with these key splicing factors at both ends of the regulated male exon. Moreover, because U2AF and the U1 snRNP are only associated transiently with the pre-mRNA during the course of spliceosome assembly, our studies are difficult to reconcile with the current model that proposes that the SEX-LETHAL blocks splicing at the second catalytic step, and instead argue that the SEX-LETHAL protein acts after splice site recognition, but before catalysis begins.

VL - 130 CP - 3 ER -