{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,31]],"date-time":"2025-10-31T19:50:00Z","timestamp":1761940200428,"version":"build-2065373602"},"reference-count":52,"publisher":"Oxford University Press (OUP)","issue":"6","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2006,3,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Motivation: A biological sequence usually has many sites whose evolution depends on other positions of the sequence, but this is not accounted for by commonly used models of sequence evolution. Here we introduce a Markov model of nucleotide sequence evolution in which the instantaneous substitution rate at a site depends on the states of other sites. Based on the concept of neighbourhood systems, our model represents a universal description of arbitrarily complex dependencies among sites.<\/jats:p>\n               <jats:p>Results: We show how to define complex models for some illustrative examples and demonstrate that our method provides a versatile resource for simulations of sequence evolution with site-specific interactions along a tree. For example, we are able to simulate the evolution of RNA taking into account both secondary structure as well as pseudoknots and other tertiary interactions. To this end, we have developed a program Simulating Site-Specific Interactions (SISSI) that simulates evolution of a nucleotide sequence along a phylogenetic tree incorporating user defined site-specific interactions. Furthermore, our method allows to simulate more complex interactions among nucleotide and other character based sequences.<\/jats:p>\n               <jats:p>Availability: We implemented our method in an ANSI C program SISSI which runs on UNIX\/Linux, Windows and Mac OS systems, including Mac OS X. SISSI is available at<\/jats:p>\n               <jats:p>Contact: \u00a0sissi@cs.uni-duesseldorf.de<\/jats:p>","DOI":"10.1093\/bioinformatics\/bti812","type":"journal-article","created":{"date-parts":[[2005,12,7]],"date-time":"2005-12-07T03:03:48Z","timestamp":1133924628000},"page":"716-722","source":"Crossref","is-referenced-by-count":28,"title":["<i>In silico<\/i> sequence evolution with site-specific interactions along phylogenetic trees"],"prefix":"10.1093","volume":"22","author":[{"given":"Tanja","family":"Gesell","sequence":"first","affiliation":[{"name":"Heinrich-Heine University Duesseldorf, Universitaetsstrasse 1 1 \u00a0 1 \u00a0 \u00a0 40225 Duesseldorf, Germany"}]},{"given":"Arndt","family":"von Haeseler","sequence":"additional","affiliation":[{"name":"Center for Integrative Bioinformatics Vienna, Max F. Perutz Laboratories 2 \u00a0 2 \u00a0 \u00a0 Dr. Bohr-Gasse 9, A-1030 Vienna, Austria"},{"name":"University of Vienna 3 \u00a0 3 \u00a0 \u00a0 Austria"},{"name":"Medical University of Vienna 4 \u00a0 4 \u00a0 \u00a0 Austria"},{"name":"University of Veterinary Medicine Vienna 5 \u00a0 5 \u00a0 \u00a0 Austria"}]}],"member":"286","published-online":{"date-parts":[[2005,12,6]]},"reference":[{"key":"2023012408534161500_b1","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1093\/bioinformatics\/16.6.501","article-title":"Phylogenetically enhanced statistical tools for RNA structure prediction","volume":"16","author":"Akmaev","year":"2000","journal-title":"Bioinformatics"},{"key":"2023012408534161500_b2","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1089\/10665270360688039","article-title":"DNA sequence evolution with neighbor-dependent mutation","volume":"10","author":"Arndt","year":"2003","journal-title":"J. Comput. Biol."},{"key":"2023012408534161500_b3","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1093\/nar\/27.1.314","article-title":"The Ribonuclease P Database","volume":"27","author":"Brown","year":"1999","journal-title":"Nucleic Acids Res."},{"key":"2023012408534161500_b4","doi-asserted-by":"crossref","first-page":"1368","DOI":"10.1093\/oxfordjournals.molbev.a025583","article-title":"Modeling residue usage in aligned protein sequences via maximum likelihood","volume":"13","author":"Bruno","year":"1996","journal-title":"Mol. Biol. Evol."},{"key":"2023012408534161500_b5","doi-asserted-by":"crossref","first-page":"1678","DOI":"10.1126\/science.273.5282.1678","article-title":"Crystal structure of a group I ribozyme domain: principles of RNA packing","volume":"273","author":"Cate","year":"1996","journal-title":"Science"},{"key":"2023012408534161500_b6","first-page":"347","article-title":"Inferring consensus structure from nucleic acid sequences","volume":"7","author":"Chiu","year":"1991","journal-title":"Comput. Appl. Biosci."},{"key":"2023012408534161500_b7","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":"2023012408534161500_b8","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1093\/genetics\/149.1.445","article-title":"Assessing the impact of secondary structure and solvent accessibility on protein evolution","volume":"149","author":"Goldman","year":"1998","journal-title":"Genetics"},{"key":"2023012408534161500_b9","first-page":"583","article-title":"Displaying the information contents of structural RNA alignments: the structure logos","volume":"13","author":"Gorodkin","year":"1997","journal-title":"CABIOS"},{"key":"2023012408534161500_b10","first-page":"559","article-title":"PSeq-Gen: an application for the Monte Carlo simulation of protein sequence evolution along phylogenetic trees","volume":"13","author":"Grassly","year":"1997","journal-title":"Comput. Appl. Biosci."},{"key":"2023012408534161500_b11","doi-asserted-by":"crossref","first-page":"5785","DOI":"10.1093\/nar\/20.21.5785","article-title":"Identifying constraints on the higher-order structure of RNA: continued development and application of comparative sequence analysis methods","volume":"20","author":"Gutell","year":"1992","journal-title":"Nucleic Acid Res."},{"key":"2023012408534161500_b12","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1089\/cmb.1998.5.149","article-title":"Evolution of DNA or amino acid sequences with dependent sites","volume":"5","author":"von Haeseler","year":"1998","journal-title":"J. Comput. Biol."},{"key":"2023012408534161500_b13","doi-asserted-by":"crossref","first-page":"910","DOI":"10.1093\/oxfordjournals.molbev.a025995","article-title":"Evolutionary distances for protein-coding sequences: modeling site-specific residue frequencies","volume":"15","author":"Halpern","year":"1998","journal-title":"Mol. Biol. Evol."},{"key":"2023012408534161500_b14","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1007\/BF02101694","article-title":"Dating of the human-ape splitting by a molecular clock of mitochondrial DNA","volume":"22","author":"Hasegawa","year":"1985","journal-title":"J. Mol. Evol."},{"key":"2023012408534161500_b15","doi-asserted-by":"crossref","first-page":"1059","DOI":"10.1016\/S0022-2836(02)00308-X","article-title":"Secondary structure prediction for aligned RNA sequences","volume":"319","author":"Hofacker","year":"2002","journal-title":"J. Mol. Biol."},{"key":"2023012408534161500_b16","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1007\/BF00818163","article-title":"Fast folding and comparison of RNA secondary structures","volume":"125","author":"Hofacker","year":"1994","journal-title":"Monatsh Chem."},{"key":"2023012408534161500_b17","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1016\/S1055-7903(03)00061-7","article-title":"RNA-based phylogenetic methods: application to mammalian mitochondrial RNA sequences","volume":"28","author":"Hudelot","year":"2003","journal-title":"Mol. Phylogenet. Evol."},{"key":"2023012408534161500_b18","doi-asserted-by":"crossref","first-page":"17","DOI":"10.2307\/2413481","article-title":"The performance of phylogenetic methods in simulation","volume":"44","author":"Huelsenbeck","year":"1995","journal-title":"Syst. Biol."},{"key":"2023012408534161500_b19","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1239\/aap\/1013540176","article-title":"Probabilistic models of DNA sequence evolution with context dependent rates of substitution","volume":"32","author":"Jensen","year":"2000","journal-title":"Adv. Appl. Prob."},{"key":"2023012408534161500_b20","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":"2023012408534161500_b21","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1007\/BF01731581","article-title":"A simple method for estimating evolutionary rates of base substitutions through comparative studies of nucleotide sequences","volume":"16","author":"Kimura","year":"1980","journal-title":"J. Mol. Evol."},{"key":"2023012408534161500_b22","doi-asserted-by":"crossref","first-page":"3423","DOI":"10.1093\/nar\/gkg614","article-title":"Pfold: RNA secondary structure prediction using stochastic context-free grammars","volume":"31","author":"Knudsen","year":"2003","journal-title":"Nucleic Acids Res."},{"key":"2023012408534161500_b23","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1093\/bioinformatics\/bti079","article-title":"HyPhy: hypothesis testing using phylogenies","volume":"21","author":"Kosakovsky Pond","year":"2005","journal-title":"Bioinformatics"},{"key":"2023012408534161500_b24","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1093\/protein\/8.7.641","article-title":"Context dependent optimal substitution matrices","volume":"8","author":"Koshi","year":"1995","journal-title":"Protein Eng."},{"key":"2023012408534161500_b25","doi-asserted-by":"crossref","first-page":"336","DOI":"10.1002\/(SICI)1097-0134(199703)27:3<336::AID-PROT2>3.0.CO;2-B","article-title":"Mutation matrices and physical-chemical properties: correlations and implications","volume":"27","author":"Koshi","year":"1997","journal-title":"Proteins"},{"key":"2023012408534161500_b26","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":"2023012408534161500_b27","doi-asserted-by":"crossref","first-page":"4208","DOI":"10.1093\/nar\/27.21.4208","article-title":"ConStruct: a tool for thermodynamic controlled prediction of conserved secondary structure","volume":"27","author":"Lueck","year":"1999","journal-title":"Nucleic Acid Res."},{"key":"2023012408534161500_b28","doi-asserted-by":"crossref","first-page":"I216","DOI":"10.1093\/bioinformatics\/bth901","article-title":"A nucleotide substitution model with nearest-neighbour interactions","volume":"20","author":"Lunter","year":"2004","journal-title":"Bioinformatics"},{"key":"2023012408534161500_b29","doi-asserted-by":"crossref","first-page":"1429","DOI":"10.1093\/genetics\/139.3.1429","article-title":"Evolutionary analyses of DNA sequences subject to constraints on secondary structure","volume":"139","author":"Muse","year":"1995","journal-title":"Genetics"},{"key":"2023012408534161500_b30","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1080\/10635150490468675","article-title":"A phyogenetic mixture model for detecting pattern-heterogeneity in gene sequence or character-state data","volume":"53","author":"Pagel","year":"2004","journal-title":"Syst. Biol."},{"key":"2023012408534161500_b31","doi-asserted-by":"crossref","first-page":"750","DOI":"10.1093\/oxfordjournals.molbev.a003857","article-title":"Structural constraints and emergence of sequence patterns in protein evolution","volume":"18","author":"Parisi","year":"2001","journal-title":"Mol. Biol. Evol."},{"key":"2023012408534161500_b32","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.gene.2004.11.025","article-title":"Generality of the structurally constrained protein evolution model: assessment on representatives of the four main fold classes","volume":"345","author":"Parisi","year":"2005","journal-title":"Gene"},{"key":"2023012408534161500_b33","doi-asserted-by":"crossref","first-page":"763","DOI":"10.1093\/oxfordjournals.molbev.a003859","article-title":"A dependent rates model and MCMC-based methodology for the maximum-likelihood analysis of sequences with overlapping reading frames","volume":"18","author":"Pedersen","year":"2001","journal-title":"Mol. Biol. Evol."},{"key":"2023012408534161500_b34","doi-asserted-by":"crossref","first-page":"1913","DOI":"10.1093\/molbev\/msh199","article-title":"An evolutionary model for protein-coding regions with conserved RNA structure","volume":"21","author":"Pedersen","year":"2004","journal-title":"Mol. Biol. Evol."},{"key":"2023012408534161500_b35","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":"2023012408534161500_b36","first-page":"235","article-title":"Seq-Gen: an application for the Monte Carlo simulation of DNA sequence evolution along phylogenetic trees","volume":"13","author":"Rambaut","year":"1997","journal-title":"Comput. Appl. Biosci."},{"key":"2023012408534161500_b37","doi-asserted-by":"crossref","first-page":"1692","DOI":"10.1093\/molbev\/msg184","article-title":"Protein evolution with dependence among codons due to tertiary structure","volume":"20","author":"Robinson","year":"2003","journal-title":"Mol. Biol. Evol."},{"key":"2023012408534161500_b38","doi-asserted-by":"crossref","first-page":"771","DOI":"10.1093\/genetics\/141.2.771","article-title":"Estimating substitution rates in ribosomal RNA genes","volume":"141","author":"Rzhetsky","year":"1995","journal-title":"Genetics"},{"key":"2023012408534161500_b39","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1093\/genetics\/157.1.399","article-title":"RNA sequence evolution with secondary structure constraints: comparison of substitution rate models using maximum-likelihood methods","volume":"157","author":"Savill","year":"2000","journal-title":"Genetics"},{"key":"2023012408534161500_b40","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1006\/mpev.1994.1026","article-title":"A stochastic model for the evolution of autocorrelated DNA sequences","volume":"3","author":"Sch\u00f6niger","year":"1994","journal-title":"Mol. Phylogenet. Evol."},{"key":"2023012408534161500_b41","first-page":"111","article-title":"Simulating efficiently the evolution of DNA sequences","volume":"11","author":"Sch\u00f6niger","year":"1995","journal-title":"Comput. Appl. Biosci."},{"key":"2023012408534161500_b42","doi-asserted-by":"crossref","first-page":"468","DOI":"10.1093\/molbev\/msh039","article-title":"Phylogenetic estimation of context-dependent substitution rates by maximum likelihood","volume":"21","author":"Siepel","year":"2004","journal-title":"Mol. Biol. Evol."},{"key":"2023012408534161500_b43","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1093\/molbev\/msh029","article-title":"Empirical models for substitution in ribosomal RNA","volume":"21","author":"Smith","year":"2004","journal-title":"Mol. Biol. Evol."},{"key":"2023012408534161500_b44","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1093\/bioinformatics\/14.2.157","article-title":"Rose: generating sequence families","volume":"14","author":"Stoye","year":"1998","journal-title":"Bioinformatics"},{"key":"2023012408534161500_b45","doi-asserted-by":"crossref","first-page":"691","DOI":"10.1093\/bioinformatics\/14.8.691","article-title":"An RNA folding method capable of identifying pseudoknots and base triples","volume":"14","author":"Tabaska","year":"1998","journal-title":"Bioinformatics"},{"key":"2023012408534161500_b46","first-page":"57","article-title":"Some probabilistic and statistical problems on the analysis of DNA sequences","volume":"17","author":"Tavar\u00e9","year":"1986","journal-title":"Lec. Math. Life Sci."},{"key":"2023012408534161500_b47","doi-asserted-by":"crossref","first-page":"666","DOI":"10.1093\/oxfordjournals.molbev.a025627","article-title":"Combining protein evolution and secondary structure","volume":"13","author":"Thorne","year":"1996","journal-title":"Mol. Biol. Evol."},{"key":"2023012408534161500_b48","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1007\/BF00160273","article-title":"Maximum likelihood with multiparameter models of substitution","volume":"39","author":"Tillier","year":"1994","journal-title":"J. Mol. Evol."},{"key":"2023012408534161500_b49","doi-asserted-by":"crossref","first-page":"1993","DOI":"10.1093\/genetics\/148.4.1993","article-title":"High apparent rate of simultaneous compensatory base-pair substitutions in ribosomal RNA","volume":"148","author":"Tillier","year":"1998","journal-title":"Genetics"},{"key":"2023012408534161500_b50","doi-asserted-by":"crossref","first-page":"1015","DOI":"10.1093\/bioinformatics\/18.7.1015","article-title":"CS-PSeq-Gen: simulating the evolution of protein sequence under constraints","volume":"18","author":"Tuff\u00e9ry","year":"2002","journal-title":"Bioinformatics"},{"key":"2023012408534161500_b51","first-page":"1396","article-title":"Maximum-likelihood estimation of phylogeny from DNA sequences when substitution rates differ over sites","volume":"10","author":"Yang","year":"1993","journal-title":"Mol. Biol. Evol."},{"key":"2023012408534161500_b52","first-page":"555","article-title":"PAML: a program package for phylogenetic analysis by maximum likelihood","volume":"13","author":"Yang","year":"2004","journal-title":"Comput. Appl. BioSci."}],"container-title":["Bioinformatics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/22\/6\/716\/48839868\/bioinformatics_22_6_716.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/22\/6\/716\/48839868\/bioinformatics_22_6_716.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,24]],"date-time":"2023-01-24T09:33:57Z","timestamp":1674552837000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article\/22\/6\/716\/294583"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2005,12,6]]},"references-count":52,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2006,3,15]]}},"URL":"https:\/\/doi.org\/10.1093\/bioinformatics\/bti812","relation":{},"ISSN":["1367-4811","1367-4803"],"issn-type":[{"type":"electronic","value":"1367-4811"},{"type":"print","value":"1367-4803"}],"subject":[],"published-other":{"date-parts":[[2006,3,15]]},"published":{"date-parts":[[2005,12,6]]}}}