{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T19:10:53Z","timestamp":1793387453401,"version":"4.5.0"},"reference-count":66,"publisher":"National Academy of Sciences","issue":"51","license":[{"start":{"date-parts":[[2025,12,16]],"date-time":"2025-12-16T00:00:00Z","timestamp":1765843200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000057","name":"HHS | NIH | National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["R35-GM150681"],"award-info":[{"award-number":["R35-GM150681"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000057","name":"HHS | NIH | National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["R01-GM74108"],"award-info":[{"award-number":["R01-GM74108"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000861","name":"Burroughs Wellcome Fund","doi-asserted-by":"publisher","award":["1176659"],"award-info":[{"award-number":["1176659"]}],"id":[{"id":"10.13039\/100000861","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2025,12,23]]},"abstract":"<jats:p>\n                    Cells require highly polymorphic receptors to perform accurate self\/non-self recognition. In the amoeba\n                    <jats:italic toggle=\"yes\">\n                      <jats:italic toggle=\"yes\">Dictyostelium discoideum<\/jats:italic>\n                      ,\n                    <\/jats:italic>\n                    polymorphic TgrB1 and TgrC1 proteins are used to bind sister cells and exclude cheaters, but it remains unknown how cells continually generate their extreme genetic diversity. Here, we created a collection of chromosome-length, whole genome sequences from 10\n                    <jats:italic toggle=\"yes\">\n                      <jats:italic toggle=\"yes\">D. discoideum<\/jats:italic>\n                    <\/jats:italic>\n                    isolates and sister species to understand the evolution of the large\n                    <jats:italic toggle=\"yes\">tgr<\/jats:italic>\n                    gene family. Our dataset includes AX2-214, a widely used\n                    <jats:italic toggle=\"yes\">D. discoideum<\/jats:italic>\n                    lab strain, as well as complete genomes for two\n                    <jats:italic toggle=\"yes\">\n                      <jats:italic toggle=\"yes\">Chlamydia<\/jats:italic>\n                    <\/jats:italic>\n                    -like endosymbionts harbored within amoebae. We find that\n                    <jats:italic toggle=\"yes\">tgrB1<\/jats:italic>\n                    and\n                    <jats:italic toggle=\"yes\">C1<\/jats:italic>\n                    lie in a hypermutational hotspot, with haplotypes that undergo repeated intralocus recombination, duplications, transpositions, and inversions. These structural dynamics are highly localized adjacent to\n                    <jats:italic toggle=\"yes\">tgrB<\/jats:italic>\n                    and\n                    <jats:italic toggle=\"yes\">C<\/jats:italic>\n                    , resulting in the gain and loss of dozens of genes. The\n                    <jats:italic toggle=\"yes\">tgrBC<\/jats:italic>\n                    genes themselves frequently duplicate and recombine, leading to the rapid generation of unique\n                    <jats:italic toggle=\"yes\">tgrBC<\/jats:italic>\n                    repertoires. In the broader\n                    <jats:italic toggle=\"yes\">tgr<\/jats:italic>\n                    gene family, some genes (e.g.,\n                    <jats:italic toggle=\"yes\">tgrN<\/jats:italic>\n                    ) are single copy and syntenic across all the genomes, whereas others (e.g.,\n                    <jats:italic toggle=\"yes\">tgrA<\/jats:italic>\n                    ) prolifically duplicate at similar rates to\n                    <jats:italic toggle=\"yes\">Dictyostelium<\/jats:italic>\n                    transposons. Thus, the\n                    <jats:italic toggle=\"yes\">tgr<\/jats:italic>\n                    genes are among the most rapidly evolving families genome-wide. We propose that the intense diversification within the\n                    <jats:italic toggle=\"yes\">tgrBC<\/jats:italic>\n                    locus can help explain how these genes acquire such extreme levels of polymorphism, with parallels to the MHC immune genes in mammals and other allorecognition systems. This collection of amoeba genomes is also a useful resource for future comparative genomics and molecular evolution studies in Amoebozoa.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2520843122","type":"journal-article","created":{"date-parts":[[2025,12,16]],"date-time":"2025-12-16T16:34:46Z","timestamp":1765902886000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":8,"title":["Hypermutable hotspot enables the rapid evolution of self\/non-self recognition genes in\n                    <i>Dictyostelium<\/i>"],"prefix":"10.1073","volume":"122","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4917-9211","authenticated-orcid":false,"given":"Mische","family":"Holland","sequence":"first","affiliation":[{"name":"Department of Biological Sciences, University of Pittsburgh","place":["Pittsburgh, PA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-1998-1683","authenticated-orcid":false,"given":"Mayar","family":"Ahmed","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, University of Pittsburgh","place":["Pittsburgh, PA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8220-8427","authenticated-orcid":false,"given":"Janet M.","family":"Young","sequence":"additional","affiliation":[{"name":"Division of Basic Sciences, Fred Hutchinson Cancer Center","place":["Seattle"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James R.","family":"Drurey","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, University of Pittsburgh","place":["Pittsburgh, PA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-0863-159X","authenticated-orcid":false,"given":"Sean","family":"McFadyen","sequence":"additional","affiliation":[{"name":"School of Natural Sciences, Massey University","place":["Auckland, New Zealand"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth A.","family":"Ostrowski","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, University of Washington","place":["Bothell"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7883-8522","authenticated-orcid":false,"given":"Tera C.","family":"Levin","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, University of Pittsburgh","place":["Pittsburgh, PA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2025,12,16]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0000283"},{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1093\/molbev\/msv125"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1111\/imr.12153"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2010.11.061"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1387\/ijdb.190239gs"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1097\/00041552-199311000-00007"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-0039.2007.00834.x"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2019.07.060"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1080\/19420889.2020.1740554"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-micro-102215-095325"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1003891"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1002\/bies.200900085"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2020.04.009"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jgg.2022.03.006"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2021.102811"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms12085"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.0060287"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2009.02.037"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.8.8.948"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0124270"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.208975"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1203903"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms14171"},{"key":"e_1_3_4_24_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-48380-4"},{"key":"e_1_3_4_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2013.06.049"},{"key":"e_1_3_4_26_2","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20121674"},{"key":"e_1_3_4_27_2","doi-asserted-by":"publisher","DOI":"10.1186\/gb-2011-12-2-r20"},{"key":"e_1_3_4_28_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12038-018-9810-1"},{"key":"e_1_3_4_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2015.04.059"},{"key":"e_1_3_4_30_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1720324115"},{"key":"e_1_3_4_31_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-11237-2"},{"key":"e_1_3_4_32_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature03481"},{"key":"e_1_3_4_33_2","unstructured":"Genome. 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