{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T12:40:36Z","timestamp":1788871236677,"version":"build-2803163510"},"reference-count":40,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2014,11,19]],"date-time":"2014-11-19T00:00:00Z","timestamp":1416355200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003593","name":"CNPq","doi-asserted-by":"publisher","award":["308147\/2009-0"],"award-info":[{"award-number":["308147\/2009-0"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003593","name":"CNPq","doi-asserted-by":"publisher","award":["307982\/2012-2"],"award-info":[{"award-number":["307982\/2012-2"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003593","name":"CNPq","doi-asserted-by":"publisher","award":["481843\/2013-2"],"award-info":[{"award-number":["481843\/2013-2"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004586","name":"Faperj","doi-asserted-by":"publisher","award":["110.028\/2011"],"award-info":[{"award-number":["110.028\/2011"]}],"id":[{"id":"10.13039\/501100004586","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004586","name":"Faperj","doi-asserted-by":"publisher","award":["111.831\/2011"],"award-info":[{"award-number":["111.831\/2011"]}],"id":[{"id":"10.13039\/501100004586","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Lyssavirus is a diverse genus of viruses that infect a variety of mammalian hosts, typically causing encephalitis. The evolution of this lineage, particularly the rabies virus, has been a focus of research because of the extensive occurrence of cross-species transmission, and the distinctive geographical patterns present throughout the diversification of these viruses. Although numerous studies have examined pattern-related questions concerning Lyssavirus evolution, analyses of the evolutionary processes acting on Lyssavirus diversification are scarce. To clarify the relevance of positive natural selection in Lyssavirus diversification, we conducted a comprehensive scan for episodic diversifying selection across all lineages and codon sites of the five coding regions in lyssavirus genomes. Although the genomes of these viruses are generally conserved, the glycoprotein (G), RNA-dependent RNA polymerase (L) and polymerase (P) genes were frequently targets of adaptive evolution during the diversification of the genus. Adaptive evolution is particularly manifest in the glycoprotein gene, which was inferred to have experienced the highest density of positively selected codon sites along branches. Substitutions in the  L gene were found to be associated with the early diversification of phylogroups.  A comparison between the number of positively selected sites inferred along the branches of RABV population branches and Lyssavirus intespecies branches suggested that the occurrence of positive selection was similar on the five coding regions of the genome in both groups.<\/jats:p>","DOI":"10.3390\/v6114465","type":"journal-article","created":{"date-parts":[[2014,11,19]],"date-time":"2014-11-19T10:56:41Z","timestamp":1416394601000},"page":"4465-4478","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Analysis of Adaptive Evolution in Lyssavirus Genomes Reveals Pervasive Diversifying Selection during Species Diversification"],"prefix":"10.3390","volume":"6","author":[{"given":"Carolina","family":"Voloch","sequence":"first","affiliation":[{"name":"Department of Genetics, Federal University of Rio de Janeiro, CEP: 21941-617, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renata","family":"Capell\u00e3o","sequence":"additional","affiliation":[{"name":"Department of Genetics, Federal University of Rio de Janeiro, CEP: 21941-617, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beatriz","family":"Mello","sequence":"additional","affiliation":[{"name":"Department of Genetics, Federal University of Rio de Janeiro, CEP: 21941-617, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos","family":"Schrago","sequence":"additional","affiliation":[{"name":"Department of Genetics, Federal University of Rio de Janeiro, CEP: 21941-617, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2014,11,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"793","DOI":"10.3201\/eid1905.121071","article-title":"Novel lyssavirus in bat, Spain","volume":"19","author":"Berciano","year":"2013","journal-title":"Emerg. Infect. Dis."},{"key":"ref_2","unstructured":"King, A.M.Q., Lefkowitz, E., Adams, M.J., and Carstens, E.B. (2011). Virus Taxonomy: Ninth Report of the International Committee on Taxonomy of Viruses, Elsevier."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"7447","DOI":"10.1016\/j.vaccine.2012.10.015","article-title":"Rabies virus vaccines: Is there a need for a pan-lyssavirus vaccine?","volume":"30","author":"Evans","year":"2012","journal-title":"Vaccine"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"625","DOI":"10.20506\/rst.23.2.1514","article-title":"Rabies and rabies-related viruses: A modern perspective on an ancient disease","volume":"23","author":"Cliquet","year":"2004","journal-title":"Rev. Sci. Tech."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"e2057","DOI":"10.1371\/journal.pone.0002057","article-title":"Genomic diversity and evolution of the lyssaviruses","volume":"3","author":"Delmas","year":"2008","journal-title":"PLoS One"},{"key":"ref_6","first-page":"263","article-title":"The rabies virus genome: An overview","volume":"60","author":"Tordo","year":"1993","journal-title":"Onderstepoort J. Vet. Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1016\/j.virusres.2005.08.004","article-title":"Multiple amino acids in the glycoprotein of rabies virus are responsible for pathogenicity in adult mice","volume":"115","author":"Ito","year":"2006","journal-title":"Virus Res."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"3268","DOI":"10.1128\/JVI.75.7.3268-3276.2001","article-title":"Evidence of two Lyssavirus phylogroups with distinct pathogenicity and immunogenicity","volume":"75","author":"Badrane","year":"2001","journal-title":"J. Virol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1016\/j.meegid.2009.02.005","article-title":"The rhabdoviruses: Biodiversity, phylogenetics, and evolution","volume":"9","author":"Kuzmin","year":"2009","journal-title":"Infect. Genet. Evol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"526","DOI":"10.1006\/viro.1995.1285","article-title":"Genetic polymorphism in the rabies virus nucleoprotein gene","volume":"209","author":"Kissi","year":"1995","journal-title":"Virology"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1016\/j.virusres.2005.03.008","article-title":"Phylogenetic relationships of Irkut and West Caucasian bat viruses within the Lyssavirus genus and suggested quantitative criteria based on the N gene sequence for lyssavirus genotype definition","volume":"111","author":"Kuzmin","year":"2005","journal-title":"Virus Res."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/j.virusres.2008.04.021","article-title":"Complete genomes of Aravan, Khujand, Irkut and West Caucasian bat viruses, with special attention to the polymerase gene and non-coding regions","volume":"136","author":"Kuzmin","year":"2008","journal-title":"Virus Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1586\/14760584.3.4.333","article-title":"The challenge of new and emerging lyssaviruses","volume":"3","author":"Fooks","year":"2004","journal-title":"Expert Rev. Vaccines"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1887","DOI":"10.3201\/eid1412.080750","article-title":"Possible emergence of West Caucasian bat virus in Africa","volume":"14","author":"Kuzmin","year":"2008","journal-title":"Emerg. Infect. Dis."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"664","DOI":"10.3201\/eid1804.111553","article-title":"Ikoma lyssavirus, highly divergent novel lyssavirus in an African civet","volume":"18","author":"Marston","year":"2012","journal-title":"Emerg. Infect. Dis."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1025","DOI":"10.1099\/vir.0.061952-0","article-title":"Antigenic and genetic characterization of a divergent African virus, Ikoma lyssavirus","volume":"95","author":"Horton","year":"2014","journal-title":"J. Gen. Virol."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Holmes, E.C. (2009). The Evolution and Emergence of RNA Viruses (Oxford Series in Ecology and Evolution), Oxford University Press.","DOI":"10.1093\/oso\/9780199211128.001.0001"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2673","DOI":"10.1099\/vir.0.2008\/003913-0","article-title":"The origin and phylogeography of dog rabies virus","volume":"89","author":"Bourhy","year":"2008","journal-title":"J. Gen. Virol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1016\/B978-0-12-387040-7.00011-1","article-title":"Molecular phylogenetics of the lyssaviruses\u2013insights from a coalescent approach","volume":"79","author":"Real","year":"2011","journal-title":"Adv. Virus Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"8096","DOI":"10.1128\/JVI.75.17.8096-8104.2001","article-title":"Host switching in Lyssavirus history from the Chiroptera to the Carnivora orders","volume":"75","author":"Badrane","year":"2001","journal-title":"J. Virol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1007\/s12250-013-3334-5","article-title":"Investigation of the evolutionary history of the lyssaviruses","volume":"28","author":"Tao","year":"2013","journal-title":"Virol. Sinica"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"464","DOI":"10.1016\/j.meegid.2006.02.007","article-title":"The evolutionary history and dynamics of bat rabies virus","volume":"6","author":"Davis","year":"2006","journal-title":"Infect. Genet. Evol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"10487","DOI":"10.1128\/JVI.79.16.10487-10497.2005","article-title":"Phylogeography, population dynamics, and molecular evolution of European bat lyssaviruses","volume":"79","author":"Davis","year":"2005","journal-title":"J. Virol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1006\/viro.2001.1271","article-title":"Genetic constraints and the adaptive evolution of rabies virus in nature","volume":"292","author":"Holmes","year":"2002","journal-title":"Virology"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1016\/j.virusres.2008.04.029","article-title":"Complete genome sequence of a raccoon rabies virus isolate","volume":"136","author":"Szanto","year":"2008","journal-title":"Virus Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"568","DOI":"10.1093\/oxfordjournals.molbev.a025957","article-title":"Likelihood ratio tests for detecting positive selection and application to primate lysozyme evolution","volume":"15","author":"Yang","year":"1998","journal-title":"Mol. Biol. Evol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"908","DOI":"10.1093\/oxfordjournals.molbev.a004148","article-title":"Codon-substitution models for detecting molecular adaptation at individual sites along specific lineages","volume":"19","author":"Yang","year":"2002","journal-title":"Mol. Biol. Evol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"478","DOI":"10.1093\/molbev\/msi031","article-title":"A genetic algorithm approach to detecting lineage-specific variation in selection pressure","volume":"22","author":"Pond","year":"2005","journal-title":"Mol. Biol. Evol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"3033","DOI":"10.1093\/molbev\/msr125","article-title":"A random effects branch-site model for detecting episodic diversifying selection","volume":"28","author":"Murrell","year":"2011","journal-title":"Mol. Biol. Evol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"e1002764","DOI":"10.1371\/journal.pgen.1002764","article-title":"Detecting individual sites subject to episodic diversifying selection","volume":"8","author":"Murrell","year":"2012","journal-title":"PLoS Genet."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Yang, Z.H. (2006). Computational Molecular Evolution, Oxford University Press.","DOI":"10.1093\/acprof:oso\/9780198567028.001.0001"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"772","DOI":"10.1093\/molbev\/mst010","article-title":"MAFFT Multiple Sequence Alignment Software Version 7: Improvements in Performance and Usability","volume":"30","author":"Katoh","year":"2013","journal-title":"Mol. Biol. Evol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1093\/sysbio\/syq010","article-title":"New Algorithms and Methods to Estimate Maximum-Likelihood Phylogenies: Assessing the Performance of PhyML 3.0","volume":"59","author":"Guindon","year":"2010","journal-title":"Syst. Biol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"754","DOI":"10.1093\/bioinformatics\/17.8.754","article-title":"MRBAYES: Bayesian inference of phylogenetic trees","volume":"17","author":"Huelsenbeck","year":"2001","journal-title":"Bioinformatics"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1093\/bioinformatics\/bti079","article-title":"HyPhy: Hypothesis testing using phylogenies","volume":"21","author":"Pond","year":"2005","journal-title":"Bioinformatics"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1007\/BF02100115","article-title":"Evaluation of the maximum likelihood estimate of the evolutionary tree topologies from DNA sequence data, and the branching order in Hominoidea","volume":"29","author":"Kishino","year":"1989","journal-title":"J. Mol. Evol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"2545","DOI":"10.1099\/0022-1317-80-10-2545","article-title":"Ecology and evolution of rabies virus in Europe","volume":"80","author":"Bourhy","year":"1999","journal-title":"J. Gen. Virol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1467","DOI":"10.1099\/vir.0.80710-0","article-title":"Evolutionary timescale of rabies virus adaptation to North American bats inferred from the substitution rate of the nucleoprotein gene","volume":"86","author":"Hughes","year":"2005","journal-title":"J. Gener. Virol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"2849","DOI":"10.1099\/vir.0.81128-0","article-title":"Phylogenetic relationships among rhabdoviruses inferred using the L polymerase gene","volume":"86","author":"Bourhy","year":"2005","journal-title":"J. Gener. Virol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"950","DOI":"10.1093\/oxfordjournals.molbev.a004152","article-title":"Accuracy and power of Bayes prediction of amino acid sites under positive selection","volume":"19","author":"Anisimova","year":"2002","journal-title":"Mol. Biol. Evol."}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/6\/11\/4465\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T21:09:39Z","timestamp":1760216979000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/6\/11\/4465"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,11,19]]},"references-count":40,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2014,11]]}},"alternative-id":["v6114465"],"URL":"https:\/\/doi.org\/10.3390\/v6114465","relation":{},"ISSN":["1999-4915"],"issn-type":[{"value":"1999-4915","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,11,19]]}}}