{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T17:45:49Z","timestamp":1782409549930,"version":"3.54.5"},"reference-count":46,"publisher":"Public Library of Science (PLoS)","issue":"2","license":[{"start":{"date-parts":[[2022,2,25]],"date-time":"2022-02-25T00:00:00Z","timestamp":1645747200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["AI021423"],"award-info":[{"award-number":["AI021423"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["T32-AI007328"],"award-info":[{"award-number":["T32-AI007328"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Stanford University - Stanford Interdisciplinary Graduate Bio-X Fellowship"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>\n                    <jats:italic>Toxoplasma gondii<\/jats:italic>\n                    has numerous, large, paralogous gene families that are likely critical for supporting its unparalleled host range: nearly any nucleated cell in almost any warm-blooded animal. The\n                    <jats:italic>SRS<\/jats:italic>\n                    (SAG1-related sequence) gene family encodes over 100 proteins, the most abundant of which are thought to be involved in parasite attachment and, based on their stage-specific expression, evading the host immune response. For most SRS proteins, however, little is understood about their function and expression profile. Single-parasite RNA-sequencing previously demonstrated that across an entire population of lab-grown tachyzoites, transcripts for over 70\n                    <jats:italic>SRS<\/jats:italic>\n                    genes were detected in at least one parasite. In any one parasite, however, transcripts for an average of only 7\n                    <jats:italic>SRS<\/jats:italic>\n                    genes were detected, two of which,\n                    <jats:italic>SAG1<\/jats:italic>\n                    and\n                    <jats:italic>SAG2A<\/jats:italic>\n                    , were extremely abundant and detected in virtually all. These data do not address whether this pattern of sporadic\n                    <jats:italic>SRS<\/jats:italic>\n                    gene expression is consistently inherited among the progeny of a given parasite or arises independently of lineage. We hypothesized that if\n                    <jats:italic>SRS<\/jats:italic>\n                    expression signatures are stably inherited by progeny, subclones isolated from a cloned parent would be more alike in their expression signatures than they are to the offspring of another clone. In this report, we compare transcriptomes of clonally derived parasites to determine the degree to which expression of the SRS family is stably inherited in individual parasites. Our data indicate that in RH tachyzoites,\n                    <jats:italic>SRS<\/jats:italic>\n                    genes are variably expressed even between parasite samples subcloned from the same parent within approximately 10 parasite divisions (72 hours). This suggests that the pattern of sporadically expressed\n                    <jats:italic>SRS<\/jats:italic>\n                    genes is highly variable and not driven by inheritance mechanisms, at least under our conditions.\n                  <\/jats:p>","DOI":"10.1371\/journal.pone.0262374","type":"journal-article","created":{"date-parts":[[2022,2,25]],"date-time":"2022-02-25T13:36:26Z","timestamp":1645796186000},"page":"e0262374","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":15,"title":["Transcriptional signatures of clonally derived Toxoplasma tachyzoites reveal novel insights into the expression of a family of surface proteins"],"prefix":"10.1371","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2874-0559","authenticated-orcid":true,"given":"Terence C.","family":"Theisen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9719-745X","authenticated-orcid":true,"given":"John C.","family":"Boothroyd","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2022,2,25]]},"reference":[{"issue":"12\u201313","key":"pone.0262374.ref001","doi-asserted-by":"crossref","first-page":"1217","DOI":"10.1016\/S0020-7519(00)00124-7","article-title":"Toxoplasma gondii: from animals to humans","volume":"30","author":"AM Tenter","year":"2000","journal-title":"Int J Parasitol"},{"issue":"11","key":"pone.0262374.ref002","doi-asserted-by":"crossref","first-page":"805","DOI":"10.3109\/00365548.2012.693197","article-title":"A review on human toxoplasmosis","volume":"44","author":"G Saadatnia","year":"2012","journal-title":"Scand J Infect Dis"},{"issue":"1","key":"pone.0262374.ref003","doi-asserted-by":"crossref","first-page":"e1273865","DOI":"10.1080\/21688370.2016.1273865","article-title":"Mechanisms and pathways of Toxoplasma gondii transepithelial migration.","volume":"5","author":"EJ Jones","year":"2017","journal-title":"Tissue Barriers"},{"issue":"6","key":"pone.0262374.ref004","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1016\/S1471-4922(02)02240-7","article-title":"Is Toxoplasma egress the first step in invasion?","volume":"18","author":"EF Hoff","year":"2002","journal-title":"Trends Parasitol"},{"issue":"6","key":"pone.0262374.ref005","doi-asserted-by":"crossref","first-page":"664","DOI":"10.1093\/infdis\/126.6.664","article-title":"Toxoplasmosis and its prevention in cats and man","volume":"126","author":"JK Frenkel","year":"1972","journal-title":"J Infect Dis"},{"issue":"4","key":"pone.0262374.ref006","doi-asserted-by":"crossref","first-page":"636","DOI":"10.1084\/jem.132.4.636","article-title":"The Toxoplasma gondii oocyst from cat feces","volume":"132","author":"JP Dubey","year":"1970","journal-title":"J Exp Med"},{"issue":"3","key":"pone.0262374.ref007","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1016\/j.ijpara.2003.12.004","article-title":"The SRS superfamily of Toxoplasma surface proteins","volume":"34","author":"C Jung","year":"2004","journal-title":"Int J Parasitol"},{"issue":"6","key":"pone.0262374.ref008","doi-asserted-by":"crossref","DOI":"10.1128\/mBio.00321-12","article-title":"Integrated bioinformatic and targeted deletion analyses of the SRS gene superfamily identify SRS29C as a negative regulator of Toxoplasma virulence","volume":"3","author":"JD Wasmuth","year":"2012","journal-title":"mBio"},{"issue":"3","key":"pone.0262374.ref009","doi-asserted-by":"crossref","first-page":"574","DOI":"10.1046\/j.1365-2958.2000.02014.x","article-title":"Targeted disruption of the glycosylphosphatidylinositol-anchored surface antigen SAG3 gene in Toxoplasma gondii decreases host cell adhesion and drastically reduces virulence in mice","volume":"37","author":"F Dzierszinski","year":"2000","journal-title":"Mol Microbiol"},{"issue":"1","key":"pone.0262374.ref010","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1006\/expr.1994.1054","article-title":"Attachment of Toxoplasma gondii to host cells involves major surface protein, SAG-1 (P30).","volume":"79","author":"JR Mineo","year":"1994","journal-title":"Exp Parasitol"},{"issue":"12","key":"pone.0262374.ref011","doi-asserted-by":"crossref","first-page":"1285","DOI":"10.1016\/S0020-7519(01)00261-2","article-title":"Surface antigens of Toxoplasma gondii: variations on a theme","volume":"31","author":"C Lekutis","year":"2001","journal-title":"Int J Parasitol"},{"issue":"5","key":"pone.0262374.ref012","doi-asserted-by":"crossref","first-page":"2235","DOI":"10.1007\/s00253-018-8759-1","article-title":"Toxoplasma gondii antigen SAG2A differentially modulates IL-1beta expression in resistant and susceptible murine peritoneal cells","volume":"102","author":"JA Leal-Sena","year":"2018","journal-title":"Appl Microbiol Biotechnol"},{"issue":"9","key":"pone.0262374.ref013","doi-asserted-by":"crossref","first-page":"4444","DOI":"10.4049\/jimmunol.159.9.4444","article-title":"The surface glycoproteins of Trypanosoma cruzi encode a superfamily of variant T cell epitopes","volume":"159","author":"SJ Kahn","year":"1997","journal-title":"J Immunol"},{"issue":"8","key":"pone.0262374.ref014","first-page":"606","article-title":"Structure of the immunodominant surface antigen from the Toxoplasma gondii SRS superfamily","volume":"9","author":"XL He","year":"2002","journal-title":"Nat Struct Biol"},{"key":"pone.0262374.ref015","doi-asserted-by":"crossref","first-page":"D553","DOI":"10.1093\/nar\/gkm981","article-title":"ToxoDB: an integrated Toxoplasma gondii database resource","volume":"36","author":"B Gajria","year":"2008","journal-title":"Nucleic Acids Res"},{"key":"pone.0262374.ref016","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1186\/s12864-015-1225-x","article-title":"Asexual expansion of Toxoplasma gondii merozoites is distinct from tachyzoites and entails expression of non-overlapping gene families to attach, invade, and replicate within feline enterocytes","volume":"16","author":"AB Hehl","year":"2015","journal-title":"BMC Genomics"},{"issue":"2","key":"pone.0262374.ref017","doi-asserted-by":"crossref","first-page":"e29998","DOI":"10.1371\/journal.pone.0029998","article-title":"Transcriptomic analysis of toxoplasma development reveals many novel functions and structures specific to sporozoites and oocysts","volume":"7","author":"HM Fritz","year":"2012","journal-title":"PLoS One"},{"issue":"8","key":"pone.0262374.ref018","doi-asserted-by":"crossref","first-page":"e12354","DOI":"10.1371\/journal.pone.0012354","article-title":"Coordinated progression through two subtranscriptomes underlies the tachyzoite cycle of Toxoplasma gondii","volume":"5","author":"MS Behnke","year":"2010","journal-title":"PLoS One"},{"key":"pone.0262374.ref019","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1186\/1471-2164-15-350","article-title":"Toxoplasma gondii merozoite gene expression analysis with comparison to the life cycle discloses a unique expression state during enteric development","volume":"15","author":"MS Behnke","year":"2014","journal-title":"BMC Genomics"},{"issue":"Pt 1","key":"pone.0262374.ref020","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1017\/S0031182000066695","article-title":"Surface antigens of Toxoplasma gondii","volume":"97","author":"G Couvreur","year":"1988","journal-title":"Parasitology"},{"issue":"10","key":"pone.0262374.ref021","doi-asserted-by":"crossref","first-page":"3750","DOI":"10.1128\/iai.59.10.3750-3753.1991","article-title":"Characterization of bradyzoite-specific antigens of Toxoplasma gondii","volume":"59","author":"S Tomavo","year":"1991","journal-title":"Infect Immun"},{"issue":"4","key":"pone.0262374.ref022","doi-asserted-by":"crossref","first-page":"1632","DOI":"10.1128\/IAI.66.4.1632-1637.1998","article-title":"Expressed sequence tag analysis of the bradyzoite stage of Toxoplasma gondii: identification of developmentally regulated genes","volume":"66","author":"ID Manger","year":"1998","journal-title":"Infect Immun"},{"issue":"1","key":"pone.0262374.ref023","doi-asserted-by":"crossref","first-page":"859","DOI":"10.1186\/s12864-019-6213-0","article-title":"Proteomic and transcriptomic analyses of early and late-chronic Toxoplasma gondii infection shows novel and stage specific transcripts","volume":"20","author":"AL Garfoot","year":"2019","journal-title":"BMC Genomics"},{"issue":"1","key":"pone.0262374.ref024","doi-asserted-by":"crossref","first-page":"1474","DOI":"10.1038\/s41598-018-37671-8","article-title":"An experimental genetically attenuated live vaccine to prevent transmission of Toxoplasma gondii by cats","volume":"9","author":"C Ramakrishnan","year":"2019","journal-title":"Sci Rep"},{"issue":"1","key":"pone.0262374.ref025","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1093\/glycob\/cws134","article-title":"Toxoplasma gondii secretory proteins bind to sulfated heparin structures","volume":"23","author":"N Azzouz","year":"2013","journal-title":"Glycobiology"},{"key":"pone.0262374.ref026","first-page":"9","article-title":"A single-parasite transcriptional atlas of Toxoplasma Gondii reveals novel control of antigen expression.","author":"Y Xue","year":"2020","journal-title":"Elife"},{"issue":"2","key":"pone.0262374.ref027","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1016\/j.cell.2019.12.013","article-title":"2nd, Saeij JP, Shalek AK, Lourido S. Identification of a Master Regulator of Differentiation in Toxoplasma","volume":"180","author":"BS Waldman","year":"2020","journal-title":"Cell"},{"issue":"1","key":"pone.0262374.ref028","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1038\/nprot.2014.006","article-title":"Full-length RNA-seq from single cells using Smart-seq2.","volume":"9","author":"S Picelli","year":"2014","journal-title":"Nat Protoc"},{"issue":"1","key":"pone.0262374.ref029","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1093\/bioinformatics\/bts635","article-title":"STAR: ultrafast universal RNA-seq aligner","volume":"29","author":"A Dobin","year":"2013","journal-title":"Bioinformatics"},{"issue":"2","key":"pone.0262374.ref030","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1093\/bioinformatics\/btu638","article-title":"HTSeq\u2014a Python framework to work with high-throughput sequencing data","volume":"31","author":"S Anders","year":"2015","journal-title":"Bioinformatics"},{"issue":"3","key":"pone.0262374.ref031","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1109\/MCSE.2007.55","article-title":"Matplotlib: A 2D graphics environment","volume":"9","author":"JD Hunter","year":"2007","journal-title":"Computing in Science & Engineering"},{"issue":"7825","key":"pone.0262374.ref032","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1038\/s41586-020-2649-2","article-title":"Array programming with NumPy","volume":"585","author":"CR Harris","year":"2020","journal-title":"Nature"},{"key":"pone.0262374.ref033","first-page":"51","article-title":"Data structures for statistical computing in python","volume":"445","author":"W. McKinney","year":"2010","journal-title":"Proceedings of the 9th Python in Science Conference"},{"issue":"60","key":"pone.0262374.ref034","doi-asserted-by":"crossref","first-page":"3021","DOI":"10.21105\/joss.03021","article-title":"seaborn: statistical data visualization","volume":"6","author":"ML Waskom","year":"2021","journal-title":"Journal of Open Source Software"},{"key":"pone.0262374.ref035","volume-title":"R: A Language and Environment for Statistical Computing","author":"RC Team","year":"2020"},{"issue":"12","key":"pone.0262374.ref036","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1186\/s13059-014-0550-8","article-title":"Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2","volume":"15","author":"MI Love","year":"2014","journal-title":"Genome Biol"},{"issue":"3","key":"pone.0262374.ref037","doi-asserted-by":"crossref","DOI":"10.1128\/mBio.00182-20","article-title":"Differential Impacts on Host Transcription by ROP and GRA Effectors from the Intracellular Parasite Toxoplasma gondii","volume":"11","author":"S Rastogi","year":"2020","journal-title":"mBio"},{"issue":"9","key":"pone.0262374.ref038","doi-asserted-by":"crossref","first-page":"618","DOI":"10.1038\/nrg3542","article-title":"Single-cell sequencing-based technologies will revolutionize whole-organism science","volume":"14","author":"E Shapiro","year":"2013","journal-title":"Nat Rev Genet"},{"key":"pone.0262374.ref039","doi-asserted-by":"crossref","first-page":"10147","DOI":"10.1038\/ncomms10147","article-title":"Local admixture of amplified and diversified secreted pathogenesis determinants shapes mosaic Toxoplasma gondii genomes","volume":"7","author":"H Lorenzi","year":"2016","journal-title":"Nat Commun"},{"issue":"12","key":"pone.0262374.ref040","doi-asserted-by":"crossref","first-page":"8038","DOI":"10.4049\/jimmunol.174.12.8038","article-title":"Stage-specific expression of surface antigens by Toxoplasma gondii as a mechanism to facilitate parasite persistence","volume":"174","author":"SK Kim","year":"2005","journal-title":"J Immunol"},{"issue":"12","key":"pone.0262374.ref041","doi-asserted-by":"crossref","first-page":"e1003823","DOI":"10.1371\/journal.ppat.1003823","article-title":"The Toxoplasma gondii cyst wall protein CST1 is critical for cyst wall integrity and promotes bradyzoite persistence","volume":"9","author":"T Tomita","year":"2013","journal-title":"PLoS Pathog"},{"issue":"1","key":"pone.0262374.ref042","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1111\/j.1365-2958.2003.03967.x","article-title":"Identification of a sporozoite-specific member of the Toxoplasma SAG superfamily via genetic complementation","volume":"52","author":"JR Radke","year":"2004","journal-title":"Mol Microbiol"},{"issue":"6","key":"pone.0262374.ref043","doi-asserted-by":"crossref","first-page":"2402","DOI":"10.1128\/IAI.01494-07","article-title":"A cluster of four surface antigen genes specifically expressed in bradyzoites, SAG2CDXY, plays an important role in Toxoplasma gondii persistence","volume":"76","author":"JP Saeij","year":"2008","journal-title":"Infect Immun"},{"key":"pone.0262374.ref044","doi-asserted-by":"crossref","first-page":"806","DOI":"10.1186\/1471-2164-15-806","article-title":"Dual transcriptional profiling of mice and Toxoplasma gondii during acute and chronic infection","volume":"15","author":"KJ Pittman","year":"2014","journal-title":"BMC Genomics"},{"issue":"2","key":"pone.0262374.ref045","doi-asserted-by":"crossref","first-page":"177","DOI":"10.4049\/jimmunol.97.2.177","article-title":"Original antigenic sin in ferrets: the response to sequential infections with influenza viruses","volume":"97","author":"RG Webster","year":"1966","journal-title":"J Immunol"},{"issue":"2","key":"pone.0262374.ref046","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1089\/aid.1995.11.211","article-title":"HIV type 1 V3 region primer-induced antibody suppression is overcome by administration of C4-V3 peptides as a polyvalent immunogen","volume":"11","author":"BF Haynes","year":"1995","journal-title":"AIDS Res Hum Retroviruses"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0262374","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,27]],"date-time":"2023-01-27T18:03:54Z","timestamp":1674842634000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0262374"}},"subtitle":[],"editor":[{"given":"Zhicheng","family":"Dou","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2022,2,25]]},"references-count":46,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2022,2,25]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0262374","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2021.12.26.474199","asserted-by":"object"}]},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,2,25]]}}}