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Some of these enzymes are components of insertion sequences (IS) in the IS200\/IS605 and IS607 transposon families. Both IS families encode a TnpA transposase and a TnpB nuclease, an RNA-guided enzyme ancestral to CRISPR-Cas12s. In eukaryotes, TnpB homologs occur as two distinct types, Fanzor1s and Fanzor2s. We analyzed the evolutionary relationships between prokaryotic TnpBs and eukaryotic Fanzors, which revealed that both Fanzor1s and Fanzor2s stem from a single lineage of IS607 TnpBs with unusual active site arrangement. The widespread nature of Fanzors implies that the properties of this particular lineage of IS607 TnpBs were particularly suited to adaptation in eukaryotes. Biochemical analysis of an IS607 TnpB and Fanzor1s revealed common strategies employed by TnpBs and Fanzors to co-evolve with their cognate transposases. Collectively, our results provide a new model of sequential evolution from IS607\u00a0TnpBs to Fanzor2s, and Fanzor2s\u00a0to Fanzor1s that details how genes of prokaryotic origin evolve to give rise to new protein families in eukaryotes.<\/jats:p>","DOI":"10.1093\/nar\/gkad1053","type":"journal-article","created":{"date-parts":[[2023,11,16]],"date-time":"2023-11-16T10:45:15Z","timestamp":1700131515000},"page":"12414-12427","source":"Crossref","is-referenced-by-count":41,"title":["Eukaryotic RNA-guided endonucleases evolved from a unique clade of bacterial enzymes"],"prefix":"10.1093","volume":"51","author":[{"given":"Peter H","family":"Yoon","sequence":"first","affiliation":[{"name":"Department of Molecular and Cell Biology, University of California , Berkeley ; Berkeley , CA , USA"},{"name":"Innovative Genomics Institute; University of California , Berkeley , CA , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Petr","family":"Skopintsev","sequence":"additional","affiliation":[{"name":"Innovative Genomics Institute; 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University of California , Berkeley , CA , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evan C","family":"DeTurk","sequence":"additional","affiliation":[{"name":"Innovative Genomics Institute; University of California , Berkeley , CA , USA"},{"name":"California Institute for Quantitative Biosciences (QB3), University of California , Berkeley , CA , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zheng","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Molecular, Cell and Developmental Biology, University of California , Los Angeles,\u00a0 CA , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jasmine","family":"Amerasekera","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, University of California , Los Angeles,\u00a0 CA , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marena","family":"Trinidad","sequence":"additional","affiliation":[{"name":"Innovative Genomics Institute; University of California , Berkeley , CA , USA"},{"name":"Howard Hughes Medical Institute, University of California , Berkeley ; Berkeley,\u00a0 CA , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hunter","family":"Nisonoff","sequence":"additional","affiliation":[{"name":"Center for Computational Biology, University of California , Berkeley ; Berkeley,\u00a0CA,\u00a0 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3325-3536","authenticated-orcid":false,"given":"Kai","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cell Biology, University of California , Berkeley ; Berkeley , CA , USA"},{"name":"Innovative Genomics Institute; University of California , Berkeley , CA , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arushi","family":"Lahiri","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cell Biology, University of California , Berkeley ; Berkeley , CA , USA"},{"name":"Innovative Genomics Institute; University of California , Berkeley , CA , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ron","family":"Boger","sequence":"additional","affiliation":[{"name":"Innovative Genomics Institute; University of California , Berkeley , CA , USA"},{"name":"California Institute for Quantitative Biosciences (QB3), University of California , Berkeley , CA , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9483-138X","authenticated-orcid":false,"given":"Steve","family":"Jacobsen","sequence":"additional","affiliation":[{"name":"Department of Molecular, Cell and Developmental Biology, University of California , Los Angeles,\u00a0 CA , USA"},{"name":"Howard Hughes Medical Institute, University of California , Los Angeles\u00a0 CA , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jillian F","family":"Banfield","sequence":"additional","affiliation":[{"name":"Innovative Genomics Institute; 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