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Detailed molecular analysis of the tetracycline resistance plasmid pCW3 from<jats:italic>C. perfringens<\/jats:italic>has shown that it represents the prototype of a unique family of conjugative antibiotic resistance and virulence plasmids. We have identified the pCW3 replication region by deletion and transposon mutagenesis and showed that the essential<jats:italic>rep<\/jats:italic>gene encoded a basic protein with no similarity to any known plasmid replication proteins. An 11-gene conjugation locus containing 5 genes that encoded putative proteins with similarity to proteins from the conjugative transposon Tn<jats:italic>916<\/jats:italic>was identified, although the genes\u2019 genetic arrangements were different. Functional genetic studies demonstrated that two of the genes in this transfer clostridial plasmid (<jats:italic>tcp<\/jats:italic>) locus,<jats:italic>tcpF<\/jats:italic>and<jats:italic>tcpH<\/jats:italic>, were essential for the conjugative transfer of pCW3, and comparative analysis confirmed that the<jats:italic>tcp<\/jats:italic>locus was not confined to pCW3. The conjugation region was present on all known conjugative plasmids from<jats:italic>C. perfringens<\/jats:italic>, including an enterotoxin plasmid and other toxin plasmids. These results have significant implications for plasmid evolution, as they provide evidence that a nonreplicating Tn<jats:italic>916<\/jats:italic>-like element can evolve to become the conjugation locus of replicating plasmids that carry major virulence genes or antibiotic resistance determinants.<\/jats:p>","DOI":"10.1128\/jb.00298-06","type":"journal-article","created":{"date-parts":[[2006,6,20]],"date-time":"2006-06-20T23:15:17Z","timestamp":1150845317000},"page":"4942-4951","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":105,"title":["Functional Identification of Conjugation and Replication Regions of the Tetracycline Resistance Plasmid pCW3 from<i>Clostridium perfringens<\/i>"],"prefix":"10.1128","volume":"188","author":[{"given":"Trudi L.","family":"Bannam","sequence":"first","affiliation":[{"name":"Australian Research Council Centre of Excellence in Structural and Functional Microbial Genomics and Victorian Bioinformatics Consortium, Department of Microbiology, Monash University, Victoria 3800, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wee Lin","family":"Teng","sequence":"additional","affiliation":[{"name":"Australian Research Council Centre of Excellence in Structural and Functional Microbial Genomics and Victorian Bioinformatics Consortium, Department of Microbiology, Monash University, Victoria 3800, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dieter","family":"Bulach","sequence":"additional","affiliation":[{"name":"Australian Research Council Centre of Excellence in Structural and Functional Microbial Genomics and Victorian Bioinformatics Consortium, Department of Microbiology, Monash University, Victoria 3800, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dena","family":"Lyras","sequence":"additional","affiliation":[{"name":"Australian Research Council Centre of Excellence in Structural and Functional Microbial Genomics and Victorian Bioinformatics Consortium, Department of Microbiology, Monash University, Victoria 3800, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julian I.","family":"Rood","sequence":"additional","affiliation":[{"name":"Australian Research Council Centre of Excellence in Structural and Functional Microbial Genomics and Victorian Bioinformatics Consortium, Department of Microbiology, Monash University, Victoria 3800, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/0147-619X(85)90038-1","volume":"13","year":"1985","unstructured":"Abraham, L. 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