{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T22:25:23Z","timestamp":1778624723794,"version":"3.51.4"},"reference-count":44,"publisher":"The Royal Society","issue":"1772","license":[{"start":{"date-parts":[[2019,3,25]],"date-time":"2019-03-25T00:00:00Z","timestamp":1553472000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/royalsociety.org\/journals\/ethics-policies\/data-sharing-mining\/"}],"funder":[{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"crossref","award":["R01AI127652"],"award-info":[{"award-number":["R01AI127652"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Chan Zuckerberg Biohub"}],"content-domain":{"domain":["royalsocietypublishing.org"],"crossmark-restriction":true},"short-container-title":["Phil. Trans. R. Soc. B"],"published-print":{"date-parts":[[2019,5,13]]},"abstract":"<jats:p>\n                    CRISPR-Cas systems function as adaptive immune systems by acquiring nucleotide sequences called spacers that mediate sequence-specific defence against competitors. Uniquely, the phage ICP1 encodes a Type I-F CRISPR-Cas system that is deployed to target and overcome PLE, a mobile genetic element with anti-phage activity in\n                    <jats:italic>Vibrio cholerae<\/jats:italic>\n                    . Here, we exploit the arms race between ICP1 and PLE to examine spacer acquisition and interference under laboratory conditions to reconcile findings from wild populations. Natural ICP1 isolates encode multiple spacers directed against PLE, but we find that single spacers do not interfere equally with PLE mobilization. High-throughput sequencing to assay spacer acquisition reveals that ICP1 can also acquire spacers that target the\n                    <jats:italic>V. cholerae<\/jats:italic>\n                    chromosome. We find that targeting the\n                    <jats:italic>V. cholerae<\/jats:italic>\n                    chromosome proximal to PLE is sufficient to block PLE and is dependent on Cas2-3 helicase activity. We propose a model in which indirect chromosomal spacers are able to circumvent PLE by Cas2-3-mediated processive degradation of the\n                    <jats:italic>V. cholerae<\/jats:italic>\n                    chromosome before PLE mobilization. Generally, laboratory-acquired spacers are much more diverse than the subset of spacers maintained by ICP1 in nature, showing how evolutionary pressures can constrain CRISPR-Cas targeting in ways that are often not appreciated through\n                    <jats:italic>in vitro<\/jats:italic>\n                    analyses.\n                  <\/jats:p>\n                  <jats:p>This article is part of a discussion meeting issue \u2018The ecology and evolution of prokaryotic CRISPR-Cas adaptive immune systems\u2019.<\/jats:p>","DOI":"10.1098\/rstb.2018.0089","type":"journal-article","created":{"date-parts":[[2019,3,25]],"date-time":"2019-03-25T03:06:07Z","timestamp":1553483167000},"page":"20180089","update-policy":"https:\/\/doi.org\/10.1098\/crossmark-policy","source":"Crossref","is-referenced-by-count":49,"title":["Competition between mobile genetic elements drives optimization of a phage-encoded CRISPR-Cas system: insights from a natural arms race"],"prefix":"10.1098","volume":"374","author":[{"given":"Amelia C.","family":"McKitterick","sequence":"first","affiliation":[{"name":"Department of Plant and Microbial Biology, University of California, 111 Koshland Hall, Berkeley, CA 94720, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kristen N.","family":"LeGault","sequence":"additional","affiliation":[{"name":"Department of Plant and Microbial Biology, University of California, 111 Koshland Hall, Berkeley, CA 94720, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Angus","family":"Angermeyer","sequence":"additional","affiliation":[{"name":"Department of Plant and Microbial Biology, University of California, 111 Koshland Hall, Berkeley, CA 94720, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Munirul","family":"Alam","sequence":"additional","affiliation":[{"name":"International Centre for Diarrhoeal Disease Research, Dhaka, Bangladesh"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0139-1600","authenticated-orcid":true,"given":"Kimberley D.","family":"Seed","sequence":"additional","affiliation":[{"name":"Department of Plant and Microbial Biology, University of California, 111 Koshland Hall, Berkeley, CA 94720, USA"},{"name":"Chan Zuckerberg Biohub, San Francisco, CA 94158, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"175","published-online":{"date-parts":[[2019,3,25]]},"reference":[{"key":"e_1_3_7_2_2","doi-asserted-by":"publisher","DOI":"10.1111\/brv.12271"},{"key":"e_1_3_7_3_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-virology-031413-085500"},{"key":"e_1_3_7_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2017.11.032"},{"key":"e_1_3_7_5_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1138140"},{"key":"e_1_3_7_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/emboj.2011.41"},{"key":"e_1_3_7_7_2","doi-asserted-by":"publisher","DOI":"10.1093\/gbe\/evx192"},{"key":"e_1_3_7_8_2","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.01397-17"},{"key":"e_1_3_7_9_2","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.00227-10"},{"key":"e_1_3_7_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2012.06.003"},{"key":"e_1_3_7_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tig.2015.11.005"},{"key":"e_1_3_7_12_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.00747-15"},{"key":"e_1_3_7_13_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1006838"},{"key":"e_1_3_7_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature11927"},{"key":"e_1_3_7_15_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1192272"},{"key":"e_1_3_7_16_2","doi-asserted-by":"publisher","DOI":"10.1042\/BST20130151"},{"key":"e_1_3_7_17_2","doi-asserted-by":"crossref","first-page":"E5122","DOI":"10.1073\/pnas.1618421114","article-title":"Spacer capture and integration by a type I-F Cas1\u2013Cas2-3 CRISPR adaptation complex","volume":"114","author":"Fagerlund RD","year":"2017","journal-title":"Proc. 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