{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T02:00:43Z","timestamp":1760061643206},"reference-count":44,"publisher":"Oxford University Press (OUP)","issue":"9","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2014,5,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Motivation: The analysis of molecular coevolution provides information on the potential functional and structural implication of positions along DNA sequences, and several methods are available to identify coevolving positions using probabilistic or combinatorial approaches. The specific nucleotide or amino acid profile associated with the coevolution process is, however, not estimated, but only known profiles, such as the Watson\u2013Crick constraint, are usually considered a priori in current measures of coevolution.<\/jats:p>\n               <jats:p>Results: Here, we propose a new probabilistic model, Coev, to identify coevolving positions and their associated profile in DNA sequences while incorporating the underlying phylogenetic relationships. The process of coevolution is modeled by a 16 \u00d7 16 instantaneous rate matrix that includes rates of transition as well as a profile of coevolution. We used simulated, empirical and illustrative data to evaluate our model and to compare it with a model of \u2018independent\u2019 evolution using Akaike Information Criterion. We showed that the Coev model is able to discriminate between coevolving and non-coevolving positions and provides better specificity and specificity than other available approaches. We further demonstrate that the identification of the profile of coevolution can shed new light on the process of dependent substitution during lineage evolution.<\/jats:p>\n               <jats:p>Availability: \u00a0http:\/\/www2.unil.ch\/phylo\/bioinformatics\/coev<\/jats:p>\n               <jats:p>Contact: \u00a0nicolas.salamin@unil.ch<\/jats:p>\n               <jats:p>Supplementary information: \u00a0Supplementary data are available at Bioinformatics online.<\/jats:p>","DOI":"10.1093\/bioinformatics\/btu012","type":"journal-article","created":{"date-parts":[[2014,1,12]],"date-time":"2014-01-12T01:28:34Z","timestamp":1389490114000},"page":"1241-1249","source":"Crossref","is-referenced-by-count":28,"title":["Evolutionary footprint of coevolving positions in genes"],"prefix":"10.1093","volume":"30","author":[{"given":"Linda","family":"Dib","sequence":"first","affiliation":[{"name":"1 Department of Ecology and Evolution, University of Lausanne, 1015 Lausanne, Switzerland, 2Swiss Institute of Bioinformatics, Quartier Sorge, 1015 Lausanne, Switzerland and 3Department of Plant and Environmental Sciences, University of Gothenburg, Carl Skottsbergs gata 22B, 413 19 Gothenburg, Sweden"},{"name":"1 Department of Ecology and Evolution, University of Lausanne, 1015 Lausanne, Switzerland, 2Swiss Institute of Bioinformatics, Quartier Sorge, 1015 Lausanne, Switzerland and 3Department of Plant and Environmental Sciences, University of Gothenburg, Carl Skottsbergs gata 22B, 413 19 Gothenburg, Sweden"}]},{"given":"Daniele","family":"Silvestro","sequence":"additional","affiliation":[{"name":"1 Department of Ecology and Evolution, University of Lausanne, 1015 Lausanne, Switzerland, 2Swiss Institute of Bioinformatics, Quartier Sorge, 1015 Lausanne, Switzerland and 3Department of Plant and Environmental Sciences, University of Gothenburg, Carl Skottsbergs gata 22B, 413 19 Gothenburg, Sweden"},{"name":"1 Department of Ecology and Evolution, University of Lausanne, 1015 Lausanne, Switzerland, 2Swiss Institute of Bioinformatics, Quartier Sorge, 1015 Lausanne, Switzerland and 3Department of Plant and Environmental Sciences, University of Gothenburg, Carl Skottsbergs gata 22B, 413 19 Gothenburg, Sweden"},{"name":"1 Department of Ecology and Evolution, University of Lausanne, 1015 Lausanne, Switzerland, 2Swiss Institute of Bioinformatics, Quartier Sorge, 1015 Lausanne, Switzerland and 3Department of Plant and Environmental Sciences, University of Gothenburg, Carl Skottsbergs gata 22B, 413 19 Gothenburg, Sweden"}]},{"given":"Nicolas","family":"Salamin","sequence":"additional","affiliation":[{"name":"1 Department of Ecology and Evolution, University of Lausanne, 1015 Lausanne, Switzerland, 2Swiss Institute of Bioinformatics, Quartier Sorge, 1015 Lausanne, Switzerland and 3Department of Plant and Environmental Sciences, University of Gothenburg, Carl Skottsbergs gata 22B, 413 19 Gothenburg, Sweden"},{"name":"1 Department of Ecology and Evolution, University of Lausanne, 1015 Lausanne, Switzerland, 2Swiss Institute of Bioinformatics, Quartier Sorge, 1015 Lausanne, Switzerland and 3Department of Plant and Environmental Sciences, University of Gothenburg, Carl Skottsbergs gata 22B, 413 19 Gothenburg, Sweden"}]}],"member":"286","published-online":{"date-parts":[[2014,1,11]]},"reference":[{"key":"2023012710515288100_btu012-B1","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1093\/bioinformatics\/btg427","article-title":"Parallel metropolis coupled Markov chain Monte Carlo for Bayesian phylogenetic inference","volume":"20","author":"Altekar","year":"2004","journal-title":"Bioinformatics"},{"key":"2023012710515288100_btu012-B2","doi-asserted-by":"crossref","first-page":"e254","DOI":"10.1371\/journal.pcbi.0030254","article-title":"Analysis of sequence conservation at nucleotide resolution","volume":"3","author":"Asthana","year":"2007","journal-title":"Plos Comput. Biol."},{"key":"2023012710515288100_btu012-B3","doi-asserted-by":"crossref","first-page":"e1000488","DOI":"10.1371\/journal.pcbi.1000488","article-title":"A combinatorial approach to detect coevolved amino acid networks in protein families of variable divergence","volume":"5","author":"Baussand","year":"2009","journal-title":"Plos Comput. Biol."},{"key":"2023012710515288100_btu012-B4","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1007\/0-387-27733-1_16","article-title":"Posterior mapping and posterior predictive distributions","volume-title":"Statistical methods in molecular evolution","author":"Bollback","year":"2005"},{"key":"2023012710515288100_btu012-B5","doi-asserted-by":"crossref","first-page":"9722","DOI":"10.1073\/pnas.0400975101","article-title":"Computational inference of scenarios for alpha-proteobacterial genome evolution","volume":"101","author":"Boussau","year":"2004","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"2023012710515288100_btu012-B6","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1186\/1471-2105-3-2","article-title":"The comparative RNA web (CRW) site: an online database of comparative sequence and structure information for ribosomal, intron, and other RNAs","volume":"3","author":"Cannone","year":"2002","journal-title":"BMC Bioinform."},{"key":"2023012710515288100_btu012-B7","doi-asserted-by":"crossref","first-page":"2486","DOI":"10.1016\/j.tcs.2010.10.040","article-title":"Co-evolution and information signals in biological sequences","volume":"412","author":"Carbone","year":"2011","journal-title":"Theor. Comput. Sci."},{"key":"2023012710515288100_btu012-B8","doi-asserted-by":"crossref","first-page":"8986","DOI":"10.1073\/pnas.0900233106","article-title":"Evidence for an ancient adaptive episode of convergent molecular evolution","volume":"106","author":"Castoe","year":"2009","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"2023012710515288100_btu012-B9","doi-asserted-by":"crossref","first-page":"5691","DOI":"10.1073\/pnas.0409206102","article-title":"Directed evolution of specific receptor - ligand pairs for use in the creation of gene switches","volume":"102","author":"Chockalingam","year":"2005","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"2023012710515288100_btu012-B10","doi-asserted-by":"crossref","first-page":"1241","DOI":"10.1016\/j.cub.2007.06.036","article-title":"C4 Photosynthesis evolved in grasses via parallel adaptive genetic changes","volume":"17","author":"Christin","year":"2007","journal-title":"Curr. Biol."},{"key":"2023012710515288100_btu012-B11","doi-asserted-by":"crossref","first-page":"921","DOI":"10.1016\/j.ympev.2011.12.002","article-title":"Effect of genetic convergence on phylogenetic inference","volume":"62","author":"Christin","year":"2012","journal-title":"Mol. Phylogenet. Evol."},{"key":"2023012710515288100_btu012-B12","first-page":"5691","article-title":"Why should we care about molecular coevolution?","volume":"102","author":"Codo\u00f1er","year":"2008","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"2023012710515288100_btu012-B13","doi-asserted-by":"crossref","first-page":"W232","DOI":"10.1093\/nar\/gkt471","article-title":"CoPAP: coevolution of presenceabsence patterns","volume":"41","author":"Cohen","year":"2013","journal-title":"Nucleic Acids Res."},{"key":"2023012710515288100_btu012-B14","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1093\/aob\/mcr303","article-title":"Accelerated evolution and coevolution drove the evolutionary history of AGPase sub-units during angiosperm radiation","volume":"109","author":"Corbi","year":"2012","journal-title":"Ann. Bot-London."},{"key":"2023012710515288100_btu012-B15","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1007\/11554714_5","article-title":"Likely scenarios of intron evolution","volume-title":"Comparative Genomics","author":"Csuros","year":"2005"},{"key":"2023012710515288100_btu012-B16","doi-asserted-by":"crossref","first-page":"e48124","DOI":"10.1371\/journal.pone.0048124","article-title":"Protein fragments: functional and structural roles of their coevolution networks","volume":"7","author":"Dib","year":"2012","journal-title":"Plos One"},{"key":"2023012710515288100_btu012-B17","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1186\/1471-2148-7-214","article-title":"BEAST: Bayesian evolutionary analysis by sampling trees","volume":"7","author":"Drummond","year":"2007","journal-title":"BMC Evol. Biol."},{"key":"2023012710515288100_btu012-B18","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1093\/bib\/bbr048","article-title":"Detecting coevolving positions in a molecule: why and how to account for phylogeny","volume":"13","author":"Dutheil","year":"2012","journal-title":"Brief. Bioinform."},{"key":"2023012710515288100_btu012-B19","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1186\/1471-2148-7-242","article-title":"Detecting groups of coevolving positions in a molecule: a clustering approach","volume":"7","author":"Dutheil","year":"2007","journal-title":"BMC Evol. Biol."},{"key":"2023012710515288100_btu012-B20","doi-asserted-by":"crossref","first-page":"1919","DOI":"10.1093\/molbev\/msi183","article-title":"A model-based approach for detecting coevolving positions in a molecule","volume":"22","author":"Dutheil","year":"2005","journal-title":"Mol. Phylogenet. Evol."},{"key":"2023012710515288100_btu012-B21","doi-asserted-by":"crossref","first-page":"1868","DOI":"10.1093\/molbev\/msq069","article-title":"Base pairing constraints drive structural epistasis in ribosomal RNA sequences","volume":"27","author":"Dutheil","year":"2010","journal-title":"Mol. Phylogenet. Evol."},{"key":"2023012710515288100_btu012-B22","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1534\/genetics.105.053249","article-title":"A novel method to detect intra-molecular coevolution: adding a further dimension to selective constraints analyses","volume":"173","author":"Fares","year":"2006","journal-title":"Genetics"},{"key":"2023012710515288100_btu012-B23","doi-asserted-by":"crossref","first-page":"368","DOI":"10.1007\/BF01734359","article-title":"Evolutionary trees from DNA sequences: a maximum likelihood approach","volume":"17","author":"Felsenstein","year":"1981","journal-title":"J. Mol. Evol."},{"key":"2023012710515288100_btu012-B24","doi-asserted-by":"crossref","first-page":"1084","DOI":"10.1111\/j.2041-210X.2012.00234.x","article-title":"Diversitree: comparative phylogenetic analyses of diversification in R","volume":"3","author":"FitzJohn","year":"2012","journal-title":"Meth. Ecol. Evol."},{"key":"2023012710515288100_btu012-B25","doi-asserted-by":"crossref","first-page":"3595","DOI":"10.1111\/j.1558-5646.2012.01713.x","article-title":"Male contest competition and the coevolution of weaponry and testes in pinnipeds","volume":"66","author":"Fitzpatrick","year":"2012","journal-title":"Evolution"},{"key":"2023012710515288100_btu012-B26","first-page":"D80","article-title":"STRING v9.1: protein-protein interaction networks, with increased coverage and integration","volume":"41","author":"Franceschini","year":"2013","journal-title":"Nucleic Acids Res."},{"key":"2023012710515288100_btu012-B27","doi-asserted-by":"crossref","first-page":"7156","DOI":"10.1021\/bi050293e","article-title":"Mutual information in protein multiple sequence alignments reveals two classes of coevolving positions","volume":"44","author":"Gloor","year":"2005","journal-title":"Biochemistry"},{"key":"2023012710515288100_btu012-B28","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1002\/prot.340180402","article-title":"Correlated mutations and residue contacts in proteins","volume":"18","author":"Gobel","year":"2004","journal-title":"Proteins"},{"key":"2023012710515288100_btu012-B29","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1111\/j.1469-8137.2011.03972.x","article-title":"New grass phylogeny resolves deep evolutionary relationships and discovers C4 origins","volume":"193","author":"GPWG2","year":"2012","journal-title":"New Phytol."},{"key":"2023012710515288100_btu012-B30","doi-asserted-by":"crossref","first-page":"636","DOI":"10.1101\/gr.4746406","article-title":"The fate of laterally transferred genes: life in the fast lane to adaptation or death","volume":"16","author":"Hao","year":"2006","journal-title":"Genome Res."},{"key":"2023012710515288100_btu012-B32","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1080\/10635150390192780","article-title":"Stochastic mapping of morphological characters","volume":"52","author":"Huelsenbeck","year":"2003","journal-title":"Syst. Biol."},{"key":"2023012710515288100_btu012-B33","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/B978-1-4832-3211-9.50009-7","article-title":"Evolution of protein molecules","volume-title":"Mammalian protein metabolism","author":"Jukes","year":"1969"},{"key":"2023012710515288100_btu012-B34","doi-asserted-by":"crossref","first-page":"1095","DOI":"10.1093\/molbev\/msh112","article-title":"A Bayesian mixture model for across-site heterogeneities in the amino-acid replacement process","volume":"21","author":"Lartillot","year":"2004","journal-title":"Mol. Biol. Evol."},{"key":"2023012710515288100_btu012-B35","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1126\/science.286.5438.295","article-title":"Evolutionarily conserved pathways of energetic connectivity in protein families","volume":"286","author":"Lockless","year":"1999","journal-title":"Science"},{"key":"2023012710515288100_btu012-B36","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1186\/1471-2148-3-2","article-title":"Algorithms for computing parsimonious evolutionary scenarios for genome evolution, the last universal common ancestor and dominance of horizontal gene transfer in the evolution of prokaryotes","volume":"3","author":"Mirkin","year":"2003","journal-title":"BMC Evol. Biol."},{"key":"2023012710515288100_btu012-B37","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1093\/comjnl\/7.4.308","article-title":"A simplex method for function minimization","volume":"7","author":"Nelder","year":"1965","journal-title":"Computer J."},{"key":"2023012710515288100_btu012-B38","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1098\/rspb.1994.0006","article-title":"Detecting correlated evolution on phylogenies: a general method for the comparative analysis of discrete characters","volume":"255","author":"Pagel","year":"1994","journal-title":"Proc. B. Soc. B."},{"key":"2023012710515288100_btu012-B40","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1006\/jmbi.1998.2601","article-title":"Coevolving protein residues: maximum likelihood identification and relationship to structure","volume":"287","author":"Pollock","year":"1999","journal-title":"J. Mol. Biol."},{"key":"2023012710515288100_btu012-B41","article-title":"A Practical Approach to Phylogenetic Analysis and Hypothesis Testing","volume-title":"The Phylogenetic Handbook","author":"Ronquist","year":"2009","edition":"2nd edn"},{"key":"2023012710515288100_btu012-B42","first-page":"57","article-title":"Some probabilistic and statistical problems in the analysis of DNA sequences","volume-title":"Lectures on Mathematics in the Life Science","author":"Tavare","year":"1986"},{"key":"2023012710515288100_btu012-B43","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1186\/1471-2148-11-266","article-title":"Coevolution of amino acid residues in the key photosynthetic enzyme Rubisco","volume":"11","author":"Wang","year":"2011","journal-title":"BMC Evol. Biol."},{"key":"2023012710515288100_btu012-B44","doi-asserted-by":"crossref","first-page":"R55","DOI":"10.1016\/S0969-2126(00)00112-X","article-title":"RNA folding: beyond Watson\u2013Crick pairs","volume":"8","author":"Westhof","year":"2000","journal-title":"Structure"},{"key":"2023012710515288100_btu012-B48","doi-asserted-by":"crossref","first-page":"2119","DOI":"10.1093\/molbev\/msm142","article-title":"Detecting the coevolution of biosequences\u2013an example of RNA interaction prediction","volume":"24","author":"Yeang","year":"2007","journal-title":"Mol. Biol. Evol."},{"key":"2023012710515288100_btu012-B49","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1093\/bioinformatics\/btm584","article-title":"An integrated system for studying residue coevolution in proteins","volume":"24","author":"Yip","year":"2008","journal-title":"Bioinformatics"}],"container-title":["Bioinformatics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/30\/9\/1241\/48922934\/bioinformatics_30_9_1241.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/30\/9\/1241\/48922934\/bioinformatics_30_9_1241.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,27]],"date-time":"2023-01-27T11:31:58Z","timestamp":1674819118000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article\/30\/9\/1241\/235979"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,1,11]]},"references-count":44,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2014,5,1]]}},"URL":"https:\/\/doi.org\/10.1093\/bioinformatics\/btu012","relation":{},"ISSN":["1367-4811","1367-4803"],"issn-type":[{"value":"1367-4811","type":"electronic"},{"value":"1367-4803","type":"print"}],"subject":[],"published-other":{"date-parts":[[2014,5,1]]},"published":{"date-parts":[[2014,1,11]]}}}