{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T22:17:08Z","timestamp":1781907428636,"version":"3.54.5"},"reference-count":71,"publisher":"Oxford University Press (OUP)","issue":"11","license":[{"start":{"date-parts":[[2025,10,24]],"date-time":"2025-10-24T00:00:00Z","timestamp":1761264000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100013060","name":"European Molecular Biology Laboratory","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100013060","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,10,29]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Multinucleotide mutations simultaneously replace multiple nucleotides. They are a significant contributor to evolution and disease, as well as to misdiagnosis, misannotation and other biases in genome data analysis. Multinucleotide mutations are generally thought to be rare and random events. However, by processing over 2 million publicly shared genomes, we show that certain multinucleotide mutations are highly recurrent in SARS-CoV-2: they repeatedly and consistently modify the same multiple nucleotides at the same genome position in the same way. The most frequent of these multinucleotide mutations have independently occurred hundreds of times across all SARS-CoV-2 lineages. We find evidence that the vast majority of these recurrent multinucleotide mutations (14 out of 15, corresponding to 97.6% of all individual occurrences) are linked to transcription regulatory sequences. We propose a mechanism that can explain them through template switching as part of the natural transcription process of the virus. This previously unknown mutational pattern increases our understanding of the evolution of SARS-CoV-2 and potentially many other nidoviruses. It also has important consequences for computational evolutionary biology: we show that for example recurrent multinucleotide mutations cause approximately 12% of false positives during inference of recombination in SARS-CoV-2.<\/jats:p>","DOI":"10.1093\/molbev\/msaf272","type":"journal-article","created":{"date-parts":[[2025,10,23]],"date-time":"2025-10-23T12:29:32Z","timestamp":1761222572000},"source":"Crossref","is-referenced-by-count":2,"title":["Highly Recurrent Multinucleotide Mutations in SARS-CoV-2"],"prefix":"10.1093","volume":"42","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1776-8564","authenticated-orcid":false,"given":"Nicola","family":"De Maio","sequence":"first","affiliation":[{"name":"European Molecular Biology Laboratory-European Bioinformatics Institute, EMBL-EBI , Wellcome Genome Campus, Hinxton, Cambridgeshire CB10 1SD ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivier","family":"Anoufa","sequence":"additional","affiliation":[{"name":"European Molecular Biology Laboratory-European Bioinformatics Institute, EMBL-EBI , Wellcome Genome Campus, Hinxton, Cambridgeshire CB10 1SD ,","place":["UK"]},{"name":"Faculty of Sciences and Technologies, Universit\u00e9 de Lille, Centrale Lille, IMT Nord Europe , Lille 59000 ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0188-8289","authenticated-orcid":false,"given":"Kyle","family":"Smith","sequence":"additional","affiliation":[{"name":"Department of Electrical and Computer Engineering, University of California San Diego , San Diego, CA 92093 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5600-2900","authenticated-orcid":false,"given":"Yatish","family":"Turakhia","sequence":"additional","affiliation":[{"name":"Department of Electrical and Computer Engineering, University of California San Diego , San Diego, CA 92093 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8486-2211","authenticated-orcid":false,"given":"Nick","family":"Goldman","sequence":"additional","affiliation":[{"name":"European Molecular Biology Laboratory-European Bioinformatics Institute, EMBL-EBI , Wellcome Genome Campus, Hinxton, Cambridgeshire CB10 1SD ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2025,10,24]]},"reference":[{"key":"2025111507514557100_msaf272-B1","doi-asserted-by":"publisher","first-page":"1988","DOI":"10.1101\/gr.219956.116","article-title":"Deep sequencing of natural and experimental populations of Drosophila melanogaster reveals biases in the spectrum of new mutations","volume":"27","author":"Assaf","year":"2017","journal-title":"Genome Res"},{"key":"2025111507514557100_msaf272-B2","doi-asserted-by":"publisher","first-page":"1283","DOI":"10.1126\/science.287.5456.1283","article-title":"Evidence for a high frequency of simultaneous double-nucleotide substitutions","volume":"287","author":"Averof","year":"2000","journal-title":"Science"},{"key":"2025111507514557100_msaf272-B3","doi-asserted-by":"publisher","first-page":"558","DOI":"10.1038\/nature02601","article-title":"Positive selection at sites of multiple amino acid replacements since rat\u2013mouse divergence","volume":"429","author":"Bazykin","year":"2004","journal-title":"Nature"},{"key":"2025111507514557100_msaf272-B4","doi-asserted-by":"publisher","first-page":"105","DOI":"10.1186\/s12915-019-0727-4","article-title":"Crossing fitness valleys via double substitutions within codons","volume":"17","author":"Belinky","year":"2019","journal-title":"BMC Biol"},{"key":"2025111507514557100_msaf272-B5","doi-asserted-by":"publisher","first-page":"1382","DOI":"10.1038\/s41564-024-01655-4","article-title":"Targeted accurate RNA consensus sequencing (tARC-seq) reveals mechanisms of replication error affecting SARS-CoV-2 divergence","volume":"9","author":"Bradley","year":"2024","journal-title":"Nat Microbiol"},{"key":"2025111507514557100_msaf272-B6","doi-asserted-by":"publisher","first-page":"1560","DOI":"10.1016\/j.cell.2020.07.033","article-title":"Structural basis for helicase-polymerase coupling in the SARS-CoV-2 replication-transcription complex","volume":"182","author":"Chen","year":"2020","journal-title":"Cell"},{"key":"2025111507514557100_msaf272-B7","doi-asserted-by":"publisher","first-page":"392","DOI":"10.1002\/humu.2014.35.issue-3","article-title":"A new and more accurate estimate of the rate of concurrent tandem-base substitution mutations in the human germline: 0.4% of the single-nucleotide substitution mutation rate","volume":"35","author":"Chen","year":"2014","journal-title":"Hum Mutat"},{"key":"2025111507514557100_msaf272-B8","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1186\/s13040-021-00251-0","article-title":"Indels in SARS-CoV-2 occur at template-switching hotspots","volume":"14","author":"Chrisman","year":"2021","journal-title":"BioData Min"},{"key":"2025111507514557100_msaf272-B9","author":"De Maio"},{"key":"2025111507514557100_msaf272-B10","doi-asserted-by":"publisher","first-page":"725","DOI":"10.1093\/molbev\/mss266","article-title":"Estimating empirical codon hidden Markov models","volume":"30","author":"De Maio","year":"2013","journal-title":"Mol Biol Evol"},{"key":"2025111507514557100_msaf272-B11","author":"De Maio"},{"key":"2025111507514557100_msaf272-B12","doi-asserted-by":"publisher","first-page":"evab087","DOI":"10.1093\/gbe\/evab087","article-title":"Mutation rates and selection on synonymous mutations in SARS-CoV-2","volume":"13","author":"De Maio","year":"2021","journal-title":"Genome Biol Evol"},{"key":"2025111507514557100_msaf272-B13","doi-asserted-by":"publisher","author":"De Maio","year":"2024","DOI":"10.1101\/2024.07.12.603240"},{"key":"2025111507514557100_msaf272-B14","doi-asserted-by":"publisher","first-page":"659287","DOI":"10.3389\/fgene.2021.659287","article-title":"Watch out for a second SNP: focus on multi-nucleotide variants in coding regions and rescued stop-gained","volume":"12","author":"Degalez","year":"2021","journal-title":"Front Genet"},{"key":"2025111507514557100_msaf272-B15","doi-asserted-by":"publisher","first-page":"e1004041","DOI":"10.1371\/journal.pcbi.1004041","article-title":"Clonalframeml: efficient inference of recombination in whole bacterial genomes","volume":"11","author":"Didelot","year":"2015","journal-title":"PLoS Comput Biol"},{"key":"2025111507514557100_msaf272-B16","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1186\/s12862-018-1326-7","article-title":"Improved inference of site-specific positive selection under a generalized parametric codon model when there are multinucleotide mutations and multiple nonsynonymous rates","volume":"19","author":"Dunn","year":"2019","journal-title":"BMC Evol Biol"},{"key":"2025111507514557100_msaf272-B17","doi-asserted-by":"publisher","first-page":"300","DOI":"10.1016\/j.jmb.2005.11.071","article-title":"Cis and trans-acting effects on a mutational hotspot involving a replication template switch","volume":"356","author":"Dutra","year":"2006","journal-title":"J Mol Biol"},{"key":"2025111507514557100_msaf272-B18","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1038\/s41586-020-2739-1","article-title":"The coding capacity of SARS-CoV-2","volume":"589","author":"Finkel","year":"2021","journal-title":"Nature"},{"key":"2025111507514557100_msaf272-B19","doi-asserted-by":"publisher","first-page":"1343","DOI":"10.1038\/s42003-021-02858-9","article-title":"Template switching and duplications in SARS-CoV-2 genomes give rise to insertion variants that merit monitoring","volume":"4","author":"Garushyants","year":"2021","journal-title":"Commun Biol"},{"key":"2025111507514557100_msaf272-B20","doi-asserted-by":"publisher","first-page":"8577","DOI":"10.1073\/pnas.82.24.8577","article-title":"Sequence-directed mutagenesis: evidence from a phylogenetic history of human alpha-interferon genes","volume":"82","author":"Golding","year":"1985","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2025111507514557100_msaf272-B21","doi-asserted-by":"publisher","first-page":"gkaf503","DOI":"10.1093\/nar\/gkaf503","article-title":"The mutation rate of SARS-CoV-2 is highly variable between sites and is influenced by sequence context, genomic region, and rna structure","volume":"53","author":"Haddox","year":"2025","journal-title":"Nucleic Acids Res"},{"key":"2025111507514557100_msaf272-B22","volume-title":"Population genetics","author":"Hamilton","year":"2021","edition":"2nd ed"},{"key":"2025111507514557100_msaf272-B23","doi-asserted-by":"publisher","first-page":"471","DOI":"10.1016\/0022-2836(88)90629-8","article-title":"Multiple base-pair mutations in yeast","volume":"201","author":"Hampsey","year":"1988","journal-title":"J Mol Biol"},{"key":"2025111507514557100_msaf272-B24","doi-asserted-by":"publisher","first-page":"W619","DOI":"10.1093\/nar\/gkab417","article-title":"The COVID-19 data portal: accelerating SARS-CoV-2 and COVID-19 research through rapid open access data sharing","volume":"49","author":"Harrison","year":"2021","journal-title":"Nucleic Acids Res"},{"key":"2025111507514557100_msaf272-B25","doi-asserted-by":"publisher","first-page":"233","DOI":"10.1534\/genetics.109.110510","article-title":"Human triallelic sites: evidence for a new mutational mechanism?","volume":"184","author":"Hodgkinson","year":"2010","journal-title":"Genetics"},{"key":"2025111507514557100_msaf272-B26","doi-asserted-by":"publisher","author":"Hunt","year":"2024","DOI":"10.1101\/2024.04.29.591666"},{"key":"2025111507514557100_msaf272-B27","doi-asserted-by":"publisher","first-page":"1047","DOI":"10.1101\/gr.239756.118","article-title":"Exome-wide assessment of the functional impact and pathogenicity of multinucleotide mutations","volume":"29","author":"Kaplanis","year":"2019","journal-title":"Genome Res"},{"key":"2025111507514557100_msaf272-B29","doi-asserted-by":"publisher","first-page":"914","DOI":"10.1016\/j.cell.2020.04.011","article-title":"The architecture of SARS-CoV-2 transcriptome","volume":"181","author":"Kim","year":"2020","journal-title":"Cell"},{"key":"2025111507514557100_msaf272-B30","doi-asserted-by":"publisher","first-page":"792","DOI":"10.1101\/gr.185041.114","article-title":"Characteristics of de novo structural changes in the human genome","volume":"25","author":"Kloosterman","year":"2015","journal-title":"Genome Res"},{"key":"2025111507514557100_msaf272-B31","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1002\/(ISSN)1098-1004","article-title":"Direct estimates of human per nucleotide mutation rates at 20 loci causing mendelian diseases","volume":"21","author":"Kondrashov","year":"2003","journal-title":"Hum Mutat"},{"key":"2025111507514557100_msaf272-B32","doi-asserted-by":"publisher","first-page":"1464","DOI":"10.1093\/molbev\/msm064","article-title":"An empirical codon model for protein sequence evolution","volume":"24","author":"Kosiol","year":"2007","journal-title":"Mol Biol Evol"},{"key":"2025111507514557100_msaf272-B34","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/s00239-005-0120-5","article-title":"Searching for sequence directed mutagenesis in eukaryotes","volume":"64","author":"Ladoukakis","year":"2007","journal-title":"J Mol Evol"},{"key":"2025111507514557100_msaf272-B35","doi-asserted-by":"publisher","first-page":"108","DOI":"10.1038\/s41564-021-01019-2","article-title":"Synthetic DNA spike-ins (SDSIs) enable sample tracking and detection of inter-sample contamination in SARS-CoV-2 sequencing workflows","volume":"7","author":"Lagerborg","year":"2022","journal-title":"Nat Microbiol"},{"key":"2025111507514557100_msaf272-B36","doi-asserted-by":"publisher","first-page":"904513","DOI":"10.3389\/fgene.2022.904513","article-title":"How the replication and transcription complex functions in jumping transcription of SARS-CoV-2","volume":"13","author":"Liang","year":"2022","journal-title":"Front Genet"},{"key":"2025111507514557100_msaf272-B37","doi-asserted-by":"publisher","first-page":"1437","DOI":"10.1101\/gr.276478.121","article-title":"Thousands of human mutation clusters are explained by short-range template switching","volume":"32","author":"L\u00f6ytynoja","year":"2022","journal-title":"Genome Res"},{"key":"2025111507514557100_msaf272-B38","doi-asserted-by":"publisher","first-page":"1039","DOI":"10.1101\/gr.214973.116","article-title":"Short template switch events explain mutation clusters in the human genome","volume":"27","author":"L\u00f6ytynoja","year":"2017","journal-title":"Genome Res"},{"key":"2025111507514557100_msaf272-B39","doi-asserted-by":"publisher","first-page":"e0248337","DOI":"10.1371\/journal.pone.0248337","article-title":"Extra base hits: widespread empirical support for instantaneous multiple-nucleotide changes","volume":"16","author":"Lucaci","year":"2021","journal-title":"PLoS One"},{"key":"2025111507514557100_msaf272-B40","doi-asserted-by":"publisher","first-page":"msad150","DOI":"10.1093\/molbev\/msad150","article-title":"Evolutionary shortcuts via multinucleotide substitutions and their impact on natural selection analyses","volume":"40","author":"Lucaci","year":"2023","journal-title":"Mol Biol Evol"},{"key":"2025111507514557100_msaf272-B41","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1038\/s41580-021-00432-z","article-title":"Structures and functions of coronavirus replication\u2013transcription complexes and their relevance for SARS-CoV-2 drug design","volume":"23","author":"Malone","year":"2022","journal-title":"Nat Rev Mol Cell Biol"},{"key":"2025111507514557100_msaf272-B42","doi-asserted-by":"publisher","first-page":"361","DOI":"10.1038\/s41579-023-00878-2","article-title":"The evolution of SARS-CoV-2","volume":"21","author":"Markov","year":"2023","journal-title":"Nat Rev Microbiol"},{"key":"2025111507514557100_msaf272-B43","doi-asserted-by":"publisher","first-page":"e3002982","DOI":"10.1371\/journal.pbio.3002982","article-title":"Emergence of SARS-CoV-2 subgenomic RNAs that enhance viral fitness and immune evasion","volume":"23","author":"Mears","year":"2025","journal-title":"PLoS Biol"},{"key":"2025111507514557100_msaf272-B44","doi-asserted-by":"publisher","first-page":"360","DOI":"10.1073\/pnas.91.1.360","article-title":"Uv and skin cancer: specific p53 gene mutation in normal skin as a biologically relevant exposure measurement","volume":"91","author":"Nakazawa","year":"1994","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2025111507514557100_msaf272-B45","doi-asserted-by":"publisher","first-page":"929","DOI":"10.1093\/genetics\/148.3.929","article-title":"Likelihood models for detecting positively selected amino acid sites and applications to the HIV-1 envelope gene","volume":"148","author":"Nielsen","year":"1998","journal-title":"Genetics"},{"key":"2025111507514557100_msaf272-B46","doi-asserted-by":"publisher","first-page":"veab064","DOI":"10.1093\/ve\/veab064","article-title":"Assignment of epidemiological lineages in an emerging pandemic using the pangolin tool","volume":"7","author":"O\u2019Toole","year":"2021","journal-title":"Virus Evol"},{"key":"2025111507514557100_msaf272-B47","doi-asserted-by":"publisher","first-page":"1403","DOI":"10.1099\/vir.0.81611-0","article-title":"Nidovirus transcription: how to make sense\u2026?","volume":"87","author":"Pasternak","year":"2006","journal-title":"J Gen Virol"},{"key":"2025111507514557100_msaf272-B48","doi-asserted-by":"publisher","first-page":"1403","DOI":"10.1038\/s41564-020-0770-5","article-title":"A dynamic nomenclature proposal for SARS-CoV-2 lineages to assist genomic epidemiology","volume":"5","author":"Rambaut","year":"2020","journal-title":"Nat Microbiol"},{"key":"2025111507514557100_msaf272-B49","doi-asserted-by":"publisher","first-page":"276","DOI":"10.1016\/S0168-9525(00)02024-2","article-title":"Emboss: the European molecular biology open software suite","volume":"16","author":"Rice","year":"2000","journal-title":"Trends Genet"},{"key":"2025111507514557100_msaf272-B50","doi-asserted-by":"publisher","first-page":"401","DOI":"10.1093\/bioinformatics\/btl633","article-title":"Enrichment or depletion of a go category within a class of genes: which test?","volume":"23","author":"Rivals","year":"2006","journal-title":"Bioinformatics"},{"key":"2025111507514557100_msaf272-B51","doi-asserted-by":"publisher","first-page":"710","DOI":"10.1016\/j.molcel.2020.07.027","article-title":"Coronavirus RNA proofreading: molecular basis and therapeutic targeting","volume":"79","author":"Robson","year":"2020","journal-title":"Mol Cell"},{"key":"2025111507514557100_msaf272-B52","doi-asserted-by":"publisher","first-page":"2745","DOI":"10.1038\/s41467-022-30518-x","article-title":"Co-infection with SARS-CoV-2 omicron and delta variants revealed by genomic surveillance","volume":"13","author":"Rockett","year":"2022","journal-title":"Nat Commun"},{"key":"2025111507514557100_msaf272-B53","doi-asserted-by":"publisher","first-page":"e82392","DOI":"10.7554\/eLife.82392","article-title":"Taxonium, a web-based tool for exploring large phylogenetic trees","volume":"11","author":"Sanderson","year":"2022","journal-title":"Elife"},{"key":"2025111507514557100_msaf272-B54","doi-asserted-by":"publisher","first-page":"594","DOI":"10.1038\/s41586-023-06649-6","article-title":"A molnupiravir-associated mutational signature in global SARS-CoV-2 genomes","volume":"623","author":"Sanderson","year":"2023","journal-title":"Nature"},{"key":"2025111507514557100_msaf272-B55","doi-asserted-by":"publisher","first-page":"1051","DOI":"10.1016\/j.cub.2011.05.013","article-title":"Pervasive multinucleotide mutational events in eukaryotes","volume":"21","author":"Schrider","year":"2011","journal-title":"Curr Biol"},{"key":"2025111507514557100_msaf272-B56","doi-asserted-by":"publisher","first-page":"btad538","DOI":"10.1093\/bioinformatics\/btad538","article-title":"Tracking and curating putative SARS-CoV-2 recombinants with rivet","volume":"39","author":"Smith","year":"2023","journal-title":"Bioinformatics"},{"key":"2025111507514557100_msaf272-B57","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1093\/molbev\/msg003","article-title":"A low rate of simultaneous double-nucleotide mutations in primates","volume":"20","author":"Smith","year":"2003","journal-title":"Mol Biol Evol"},{"key":"2025111507514557100_msaf272-B58","doi-asserted-by":"publisher","first-page":"282","DOI":"10.1158\/0008-5472.CAN-20-2151","article-title":"Misannotated multi-nucleotide variants in public cancer genomics datasets lead to inaccurate mutation calls with significant implications","volume":"81","author":"Srinivasan","year":"2021","journal-title":"Cancer Res"},{"key":"2025111507514557100_msaf272-B59","doi-asserted-by":"publisher","first-page":"e1009175","DOI":"10.1371\/journal.pgen.1009175","article-title":"Stability of SARS-CoV-2 phylogenies","volume":"16","author":"Turakhia","year":"2020","journal-title":"PLoS Genet"},{"key":"2025111507514557100_msaf272-B60","doi-asserted-by":"publisher","first-page":"994","DOI":"10.1038\/s41586-022-05189-9","article-title":"Pandemic-scale phylogenomics reveals the SARS-CoV-2 recombination landscape","volume":"609","author":"Turakhia","year":"2022","journal-title":"Nature"},{"key":"2025111507514557100_msaf272-B61","doi-asserted-by":"publisher","first-page":"3475","DOI":"10.1093\/nar\/gkac144","article-title":"Nanopore recappable sequencing maps SARS-CoV-2 5\u2032 capping sites and provides new insights into the structure of sgRNAs","volume":"50","author":"Ugolini","year":"2022","journal-title":"Nucleic Acids Res"},{"key":"2025111507514557100_msaf272-B62","doi-asserted-by":"publisher","first-page":"1280","DOI":"10.1038\/s41559-018-0584-5","article-title":"Multinucleotide mutations cause false inferences of lineage-specific positive selection","volume":"2","author":"Venkat","year":"2018","journal-title":"Nat Ecol Evol"},{"key":"2025111507514557100_msaf272-B63","doi-asserted-by":"publisher","first-page":"261","DOI":"10.1038\/s41592-019-0686-2","article-title":"Scipy 1.0: fundamental algorithms for scientific computing in python","volume":"17","author":"Virtanen","year":"2020","journal-title":"Nat Methods"},{"key":"2025111507514557100_msaf272-B64","doi-asserted-by":"publisher","first-page":"155","DOI":"10.1038\/s41579-020-00468-6","article-title":"Coronavirus biology and replication: implications for SARS-CoV-2","volume":"19","author":"V\u2019kovski","year":"2021","journal-title":"Nat Rev Microbiol"},{"key":"2025111507514557100_msaf272-B65","doi-asserted-by":"publisher","first-page":"145","DOI":"10.12688\/wellcomeopenres","article-title":"Misannotation of multiple-nucleotide variants risks misdiagnosis","volume":"4","author":"Wakeling","year":"2019","journal-title":"Wellcome Open Res"},{"key":"2025111507514557100_msaf272-B66","doi-asserted-by":"publisher","first-page":"e1009221","DOI":"10.1371\/journal.pgen.1009221","article-title":"Short-range template switching in great ape genomes explored using pair hidden Markov models","volume":"17","author":"Walker","year":"2021","journal-title":"PLoS Genet"},{"key":"2025111507514557100_msaf272-B67","doi-asserted-by":"publisher","first-page":"zcac043","DOI":"10.1093\/narcan\/zcac043","article-title":"Pancan-MNVQTLdb: systematic identification of multi-nucleotide variant quantitative trait loci in 33 cancer types","volume":"4","author":"Wang","year":"2022","journal-title":"NAR Cancer"},{"key":"2025111507514557100_msaf272-B68","doi-asserted-by":"publisher","first-page":"2539","DOI":"10.1038\/s41467-019-12438-5","article-title":"Landscape of multi-nucleotide variants in 125,748 human exomes and 15,708 genomes","volume":"11","author":"Wang","year":"2020","journal-title":"Nat Commun"},{"key":"2025111507514557100_msaf272-B69","doi-asserted-by":"publisher","first-page":"2027","DOI":"10.1534\/genetics.103.023226","article-title":"Estimating the frequency of events that cause multiple-nucleotide changes","volume":"167","author":"Whelan","year":"2004","journal-title":"Genetics"},{"key":"2025111507514557100_msaf272-B70","doi-asserted-by":"publisher","first-page":"265","DOI":"10.1038\/s41586-020-2008-3","article-title":"A new coronavirus associated with human respiratory disease in China","volume":"579","author":"Wu","year":"2020","journal-title":"Nature"},{"key":"2025111507514557100_msaf272-B71","doi-asserted-by":"publisher","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":"2025111507514557100_msaf272-B72","doi-asserted-by":"publisher","first-page":"303","DOI":"10.1038\/nrg3186","article-title":"Molecular phylogenetics: principles and practice","volume":"13","author":"Yang","year":"2012","journal-title":"Nat Rev Genet"},{"key":"2025111507514557100_msaf272-B73","doi-asserted-by":"publisher","first-page":"12758","DOI":"10.1038\/ncomms12758","article-title":"Morphological and molecular convergences in mammalian phylogenetics","volume":"7","author":"Zou","year":"2016","journal-title":"Nat Commun"}],"container-title":["Molecular Biology and Evolution"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/mbe\/advance-article-pdf\/doi\/10.1093\/molbev\/msaf272\/64925319\/msaf272.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/mbe\/article-pdf\/42\/11\/msaf272\/64925319\/msaf272.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/mbe\/article-pdf\/42\/11\/msaf272\/64925319\/msaf272.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,15]],"date-time":"2025-11-15T12:51:55Z","timestamp":1763211115000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/mbe\/article\/doi\/10.1093\/molbev\/msaf272\/8301027"}},"subtitle":[],"editor":[{"given":"Koichiro","family":"Tamura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2025,10,24]]},"references-count":71,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2025,10,29]]}},"URL":"https:\/\/doi.org\/10.1093\/molbev\/msaf272","relation":{},"ISSN":["0737-4038","1537-1719"],"issn-type":[{"value":"0737-4038","type":"print"},{"value":"1537-1719","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2025,11]]},"published":{"date-parts":[[2025,10,24]]},"article-number":"msaf272"}}