{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T17:09:18Z","timestamp":1779901758515,"version":"3.53.1"},"reference-count":67,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2021,11,4]],"date-time":"2021-11-04T00:00:00Z","timestamp":1635984000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pathogens"],"abstract":"<jats:p>In Europe, Babesia divergens is responsible for most of the severe cases of human babesiosis. In the present study, we describe a case of babesiosis in a splenectomized patient in France and report a detailed molecular characterization of the etiological agent, named Babesia sp. FR1, as well as of closely related Babesia divergens, Babesia capreoli and Babesia sp. MO1-like parasites. The analysis of the conserved 18S rRNA gene was supplemented with the analysis of more discriminant markers involved in the red blood cell invasion process: rap-1a (rhoptry-associated-protein 1) and ama-1 (apical-membrane-antigen 1). The rap-1a and ama-1 phylogenetic analyses were congruent, placing Babesia sp. FR1, the new European etiological agent, in the American cluster of Babesia sp. MO1-like parasites. Based on two additional markers, our analysis confirms the clear separation of B. divergens and B. capreoli. Babesia sp. MO1-like parasites should also be considered as a separate species, with the rabbit as its natural host, differing from those of B. divergens (cattle) and B. capreoli (roe deer). The natural host of Babesia sp. FR1 remains to be discovered.<\/jats:p>","DOI":"10.3390\/pathogens10111433","type":"journal-article","created":{"date-parts":[[2021,11,4]],"date-time":"2021-11-04T22:25:54Z","timestamp":1636064754000},"page":"1433","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["The New Human Babesia sp. FR1 Is a European Member of the Babesia sp. MO1 Clade"],"prefix":"10.3390","volume":"10","author":[{"given":"Claire","family":"Bonsergent","sequence":"first","affiliation":[{"name":"BIOEPAR, INRAE, Oniris, 44300 Nantes, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie-Charlotte","family":"de Carn\u00e9","sequence":"additional","affiliation":[{"name":"Service de Maladies Infectieuses et Tropicales, H\u00f4pital F. Quesnay, 78200 Mantes-la Jolie, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathalie","family":"de la Cotte","sequence":"additional","affiliation":[{"name":"BIOEPAR, INRAE, Oniris, 44300 Nantes, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fran\u00e7ois","family":"Moussel","sequence":"additional","affiliation":[{"name":"Laboratoire de Biologie M\u00e9dicale, H\u00f4pital F. Quesnay, 78200 Mantes-la-Jolie, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V\u00e9ronique","family":"Perronne","sequence":"additional","affiliation":[{"name":"Service de Maladies Infectieuses et Tropicales, H\u00f4pital F. Quesnay, 78200 Mantes-la Jolie, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurence","family":"Malandrin","sequence":"additional","affiliation":[{"name":"BIOEPAR, INRAE, Oniris, 44300 Nantes, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,11,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1788","DOI":"10.1016\/j.meegid.2012.07.004","article-title":"Babesia: A world emerging","volume":"12","author":"Schnittger","year":"2012","journal-title":"Infect. Genet. Evol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"622","DOI":"10.3201\/eid1004.030377","article-title":"Babesia divergens-like infection, Washington State","volume":"10","author":"Herwaldt","year":"2004","journal-title":"Emerg. Infect. Dis."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"643","DOI":"10.7326\/0003-4819-124-7-199604010-00004","article-title":"A fatal case of babesiosis in Missouri: Identification of another piroplasm that infects humans","volume":"124","author":"Herwaldt","year":"1996","journal-title":"Ann. Intern. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1016\/j.idc.2015.02.008","article-title":"Babesiosis","volume":"29","author":"Vannier","year":"2015","journal-title":"Infect. Dis. Clin. N. Am."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1016\/S1473-3099(14)71046-1","article-title":"Epidemiological, clinical, and laboratory characteristics of 48 cases of \u201cBabesia venatorum\u201d infection in China: A descriptive study","volume":"15","author":"Jiang","year":"2015","journal-title":"Lancet Infect. Dis."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"959","DOI":"10.1080\/22221751.2019.1635431","article-title":"Babesia divergens in human in Gansu province, China","volume":"8","author":"Wang","year":"2019","journal-title":"Emerg. Microbes Infect."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1110","DOI":"10.1093\/cid\/ciy212","article-title":"Human babesiosis caused by a Babesia crassa-like pathogen: A case series","volume":"67","author":"Jia","year":"2018","journal-title":"Clin. Infect. Dis."},{"key":"ref_8","first-page":"11","article-title":"Piroplasmosis in man; report of a case","volume":"9","author":"Skrabalo","year":"1957","journal-title":"Doc. Med. Geogr. Trop."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/j.ijmm.2006.01.029","article-title":"Identity of the causal agents of human babesiosis in Europe","volume":"296","author":"Gray","year":"2006","journal-title":"Int. J. Med. Microbiol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"945","DOI":"10.1016\/S0248-8663(97)80114-2","article-title":"Human babesiosis in 1997","volume":"18","author":"Uguen","year":"1997","journal-title":"Rev. Med. Interne"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"942","DOI":"10.3201\/eid0908.020748","article-title":"Molecular characterization of a non-Babesia divergens organism causing zoonotic babesiosis in Europe","volume":"9","author":"Herwaldt","year":"2003","journal-title":"Emerg. Infect. Dis."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1016\/j.ijmm.2007.01.002","article-title":"First case of human babesiosis in Germany\u2014Clinical presentation and molecular characterisation of the pathogen","volume":"297","author":"Tenter","year":"2007","journal-title":"Int. J. Med. Microbiol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1007\/s00277-017-3220-6","article-title":"Low-virulent Babesia venatorum infection masquerading as hemophagocytic syndrome","volume":"97","author":"Lazarevic","year":"2018","journal-title":"Ann. Hematol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"tax073","DOI":"10.1093\/jtm\/tax073","article-title":"Case report of the patient source of the Babesia microti R1 reference strain and implications for travelers","volume":"25","author":"Stahl","year":"2018","journal-title":"J. Travel. Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"595","DOI":"10.1007\/s10096-007-0333-1","article-title":"First confirmed autochthonous case of human Babesia microti infection in Europe","volume":"26","author":"Hildebrandt","year":"2007","journal-title":"Eur. J. Clin. Microbiol. Infect. Dis."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"760","DOI":"10.1046\/j.1365-3156.2003.01074.x","article-title":"A fatal case of human babesiosis in Portugal: Molecular and phylogenetic analysis","volume":"8","author":"Parreira","year":"2003","journal-title":"Trop. Med. Int. Health."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1007\/s10096-004-1270-x","article-title":"Role of quinine in life-threatening Babesia divergens infection successfully treated with clindamycin","volume":"24","author":"Corpelet","year":"2005","journal-title":"Eur. J. Clin. Microbiol. Infect. Dis."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1116","DOI":"10.3201\/eid1607.091905","article-title":"Fatal babesiosis in man, Finland, 2004","volume":"16","author":"Haapasalo","year":"2010","journal-title":"Emerg. Infect. Dis."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"724","DOI":"10.3201\/eid2004.131409","article-title":"Severe babesiosis in immunocompetent man, Spain, 2011","volume":"20","author":"Gonzalez","year":"2014","journal-title":"Emerg. Infect. Dis."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1016\/j.ijid.2015.02.005","article-title":"First report of Babesia divergens infection in an HIV patient","volume":"33","author":"Castro","year":"2015","journal-title":"Int. J. Infect. Dis."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/j.ijid.2015.07.019","article-title":"A case of severe babesiosis treated successfully with exchange transfusion","volume":"38","author":"Tanyel","year":"2015","journal-title":"Int. J. Infect. Dis."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1016\/j.ttbdis.2017.02.016","article-title":"Splenic dysfunction from celiac disease resulting in severe babesiosis","volume":"8","author":"Lyons","year":"2017","journal-title":"Ticks Tick Borne Dis."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"730","DOI":"10.1016\/j.ttbdis.2018.02.018","article-title":"A fatal case of Babesia divergens infection in Northwestern Spain","volume":"9","author":"Asensi","year":"2018","journal-title":"Ticks Tick Borne Dis."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"101262","DOI":"10.1016\/j.ttbdis.2019.07.006","article-title":"Severe babesiosis caused by Babesia divergens in a host with intact spleen, Russia, 2018","volume":"10","author":"Kukina","year":"2019","journal-title":"Ticks Tick Borne Dis."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/j.ijid.2014.12.034","article-title":"Severe human Babesia divergens infection in Norway","volume":"33","author":"Holmaas","year":"2015","journal-title":"Int. J. Infect. Dis."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"e00414","DOI":"10.1016\/j.idcr.2018.e00414","article-title":"Fatal human babesiosis caused by Babesia divergens in an asplenic host","volume":"13","author":"Kukina","year":"2018","journal-title":"IDCases"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1","DOI":"10.14411\/fp.2020.031","article-title":"The first human case of babesiosis mimicking Reiter\u2019s syndrome","volume":"67","author":"Strizova","year":"2020","journal-title":"Folia Parasitol."},{"key":"ref_28","first-page":"111","article-title":"Human babesiosis: First case report in Switzerland","volume":"114","author":"Loutan","year":"1994","journal-title":"Rev. Med. Suisse Romande"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"114","DOI":"10.3201\/eid1701.100737","article-title":"Babesiosis in immunocompetent patients, Europe","volume":"17","author":"Martinot","year":"2011","journal-title":"Emerg. Infect. Dis."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1016\/j.medmal.2019.08.007","article-title":"Human babesiosis in Alsace","volume":"50","author":"Paleau","year":"2020","journal-title":"Med. Mal. Infect."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"96.e1","DOI":"10.1016\/j.cmi.2014.07.004","article-title":"A retrospective serological survey on human babesiosis in Belgium","volume":"21","author":"Lempereur","year":"2015","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1121","DOI":"10.3201\/eid1107.040724","article-title":"Cervids as Babesiae hosts, Slovenia","volume":"11","author":"Duh","year":"2005","journal-title":"Emerg. Infect. Dis."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1016\/j.ijpara.2009.08.008","article-title":"Redescription of Babesia capreoli (Enigk and Friedhoff, 1962) from roe deer (Capreolus capreolus): Isolation, cultivation, host specificity, molecular characterisation and differentiation from Babesia divergens","volume":"40","author":"Malandrin","year":"2010","journal-title":"Int. J. Parasitol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"697","DOI":"10.1056\/NEJM200208293470921","article-title":"Acute babesiosis caused by Babesia divergens in a resident of Kentucky","volume":"347","author":"Beattie","year":"2002","journal-title":"N. Engl. J. Med."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1622","DOI":"10.1093\/cid\/cix216","article-title":"Possible transfusion-transmitted Babesia divergens-like\/MO1 infection in an Arkansas patient","volume":"64","author":"Burgess","year":"2017","journal-title":"Clin. Infect. Dis."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1558","DOI":"10.3201\/eid2408.180309","article-title":"Probable locally acquired Babesia divergens-like infection in woman, Michigan, USA","volume":"24","author":"Herc","year":"2018","journal-title":"Emerg. Infect. Dis."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"455","DOI":"10.4269\/ajtmh.2003.69.455","article-title":"Enzootic transmission of Babesia divergens among cottontail rabbits on Nantucket Island, Massachusetts","volume":"69","author":"Goethert","year":"2003","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"3995","DOI":"10.1128\/JCM.43.8.3995-4001.2005","article-title":"In vitro cultivation of a zoonotic Babesia sp. isolated from eastern cottontail rabbits (Sylvilagus floridanus) on Nantucket Island, Massachusetts","volume":"43","author":"Holman","year":"2005","journal-title":"J. Clin. Microbiol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"865","DOI":"10.4269\/ajtmh.2005.73.865","article-title":"Comparative infectivity of Babesia divergens and a zoonotic Babesia divergens-like parasite in cattle","volume":"73","author":"Holman","year":"2005","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1645\/GE-662R.1","article-title":"In vitro host erythrocyte specificity and differential morphology of Babesia divergens and a zoonotic Babesia sp. from eastern cottontail rabbits (Sylvilagus floridanus)","volume":"92","author":"Spencer","year":"2006","journal-title":"J. Parasitol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"518","DOI":"10.1196\/annals.1373.077","article-title":"Phylogenetic and biologic evidence that Babesia divergens is not endemic in the United States","volume":"1081","author":"Holman","year":"2006","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1057","DOI":"10.1007\/s15010-013-0526-8","article-title":"Human babesiosis in Europe: What clinicians need to know","volume":"41","author":"Hildebrandt","year":"2013","journal-title":"Infection"},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Hildebrandt, A., Zintl, A., Montero, E., Hunfeld, K.P., and Gray, J. (2021). Human Babesiosis in Europe. Pathogens, 10.","DOI":"10.3390\/pathogens10091165"},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Jahfari, S., Hofhuis, A., Fonville, M., van der Giessen, J., van Pelt, W., and Sprong, H. (2016). Molecular Detection of tick-borne pathogens in humans with tick bites and erythema migrans, in the Netherlands. PLoS Negl. Trop. Dis., 10.","DOI":"10.1371\/journal.pntd.0005042"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1016\/j.exppara.2015.04.024","article-title":"Babesia divergens apical membrane antigen-1 (BdAMA-1): A poorly polymorphic protein that induces a weak and late immune response","volume":"155","author":"Moreau","year":"2015","journal-title":"Exp. Parasitol."},{"key":"ref_46","unstructured":"Sun, Y. (2010). Caract\u00e9risation mol\u00e9culaire, localisation cellulaire et conservation des prot\u00e9ines impliqu\u00e9es dans le processus d\u2019invasion des \u00e9rythrocytes par Babesia divergens. [Ph.D. Thesis, Nantes University]."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"416","DOI":"10.7589\/0090-3558-48.2.416","article-title":"Antibody prevalence and molecular identification of Babesia spp. in roe deer in France","volume":"48","author":"Bastian","year":"2012","journal-title":"J. Wildl. Dis."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1016\/j.ijpara.2018.11.007","article-title":"Human babesiosis","volume":"49","author":"Krause","year":"2019","journal-title":"Int. J. Parasitol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1080\/00034983.1998.11813307","article-title":"Human babesiosis","volume":"92","author":"Gorenflot","year":"1998","journal-title":"Ann. Trop. Med. Parasitol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1136\/vr.136.2.36","article-title":"Large scale survey of bovine babesiosis due to Babesia divergens in France","volume":"136","author":"Chauvin","year":"1995","journal-title":"Vet. Rec."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/j.vetpar.2011.10.022","article-title":"A Vegetation Index qualifying pasture edges is related to Ixodes ricinus density and to Babesia divergens seroprevalence in dairy cattle herds","volume":"185","author":"Agoulon","year":"2012","journal-title":"Vet. Parasitol."},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Gonz\u00e1lez, L.M., Estrada, K., Grande, R., Jim\u00e9nez-Jacinto, V., Vega-Alvarado, L., Sevilla, E., Barrera, J., Cuesta, I., Zaballos, \u00c1., and Bautista, J.M. (2019). Comparative and functional genomics of the protozoan parasite Babesia divergens highlighting the invasion and egress processes. PLoS Negl. Trop. Dis., 13.","DOI":"10.1371\/journal.pntd.0007680"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1398","DOI":"10.3201\/eid2008.130061","article-title":"Sika deer carrying Babesia parasites closely related to B. divergens, Japan","volume":"20","author":"Tsuji","year":"2014","journal-title":"Emerg. Infect. Dis."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"e02491-17","DOI":"10.1128\/AEM.02491-17","article-title":"The Babesia divergens Asia lineage is maintained through enzootic cycles between Ixodes persulcatus and sika deer in Hokkaido, Japan","volume":"84","author":"Tsuji","year":"2018","journal-title":"Appl. Environ. Microbiol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1051\/vetres:2003047","article-title":"Isolation of Babesia divergens from carrier cattle blood using in vitro culture","volume":"35","author":"Malandrin","year":"2004","journal-title":"Vet. Res."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1016\/0166-6851(93)90194-3","article-title":"Characterisation of a family of multi-copy genes encoding rhoptry protein homologues in Babesia bovis, Babesia ovis and Babesia canis","volume":"57","author":"Dalrymple","year":"1993","journal-title":"Mol. Biochem. Parasitol."},{"key":"ref_57","first-page":"215","article-title":"Structure, sequence, and transcriptional analysis of the Babesia bovis rap-1 multigene locus","volume":"93","author":"Suarez","year":"1998","journal-title":"Mol. Biochem. Parasitol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/S0166-6851(02)00311-0","article-title":"Organization transcription, and expression of rhoptry associated protein genes in the Babesia bigemina rap-1 locus","volume":"127","author":"Suarez","year":"2003","journal-title":"Mol. Biochem. Parasitol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1016\/j.vetpar.2013.08.025","article-title":"Sequence and organization of the rhoptry-associated-protein-1 (rap-1) locus for the sheep hemoprotozoan Babesia sp. BQ1 Lintan (B. motasi phylogenetic group)","volume":"198","author":"Niu","year":"2013","journal-title":"Vet. Parasitol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.meegid.2014.08.028","article-title":"Strong conservation of rhoptry-associated-protein-1 (RAP-1) locus organization and sequence among Babesia isolates infecting sheep from China (Babesia motasi-like phylogenetic group)","volume":"28","author":"Niu","year":"2014","journal-title":"Infect. Genet. Evol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1016\/j.vetpar.2015.04.030","article-title":"Rhoptry-associated protein (rap-1) genes in the sheep pathogen Babesia sp. Xinjiang: Multiple transcribed copies differing by 3\u2032 end repeated sequences","volume":"211","author":"Niu","year":"2015","journal-title":"Vet. Parasitol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/0166-6851(96)02570-4","article-title":"Molecular cloning of a putative rhoptry associated protein homologue from Babesia divergens","volume":"77","author":"Skuce","year":"1996","journal-title":"Mol. Biochem. Parasitol."},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Rodriguez, M., Alhassan, A., Ord, R.L., Cursino-Santos, J.R., Singh, M., Gray, J., and Lobo, C.A. (2014). Identification and characterization of the RouenBd1987 Babesia divergens Rhopty-Associated Protein 1. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0107727"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1016\/j.vetpar.2010.12.021","article-title":"Molecular cloning and genetic polymorphism of Babesia capreoli gene Bcp37\/41, an ortholog of Babesia divergens merozoite surface antigen Bd37","volume":"178","author":"Sun","year":"2011","journal-title":"Vet. Parasitol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1547","DOI":"10.1093\/molbev\/msy096","article-title":"MEGA X: Molecular evolutionary genetics analysis across computing platforms","volume":"35","author":"Kumar","year":"2018","journal-title":"Mol. Biol. Evol."},{"key":"ref_66","first-page":"678","article-title":"Estimation of the number of nucleotide substitutions when there are strong transition-transversion and G + C-content biases","volume":"9","author":"Tamura","year":"1992","journal-title":"Mol. Biol. Evol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1007\/BF01731581","article-title":"A simple method for estimating evolutionary rate of base substitutions through comparative studies of nucleotide sequences","volume":"16","author":"Kimura","year":"1980","journal-title":"J. Mol. Evol."}],"container-title":["Pathogens"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-0817\/10\/11\/1433\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:26:01Z","timestamp":1760167561000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-0817\/10\/11\/1433"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,11,4]]},"references-count":67,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2021,11]]}},"alternative-id":["pathogens10111433"],"URL":"https:\/\/doi.org\/10.3390\/pathogens10111433","relation":{},"ISSN":["2076-0817"],"issn-type":[{"value":"2076-0817","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,11,4]]}}}