{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T14:11:17Z","timestamp":1785161477102,"version":"3.55.0"},"posted":{"date-parts":[[2026,4,12]]},"group-title":"Genetics","reference-count":65,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,4,12]],"date-time":"2026-04-12T00:00:00Z","timestamp":1775952000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"crossref","award":["R35GM146871"],"award-info":[{"award-number":["R35GM146871"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000001","name":"U.S. National Science Foundation","doi-asserted-by":"crossref","award":["1756912"],"award-info":[{"award-number":["1756912"]}],"id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"crossref"}]},{"name":"UW-Madison Alumni Foundation Hiroshi-Sugiyama Fund"},{"name":"UW-Madison Bacteriology Department Peterson Fellowship"},{"DOI":"10.13039\/100012627","name":"NASA Astrobiology Institute","doi-asserted-by":"crossref","award":["NNH23ZDA001N-EXO"],"award-info":[{"award-number":["NNH23ZDA001N-EXO"]}],"id":[{"id":"10.13039\/100012627","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,7,22]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Disruptions in purine metabolism contribute to a range of human diseases, from rare genetic disorders such as Lesch-Nyhan syndrome and xanthinuria to common conditions including gout and cancer. To better understand the metabolic networks that regulate purine homeostasis, we developed a\n                  <jats:italic>Caenorhabditis elegans<\/jats:italic>\n                  model of xanthine dehydrogenase (\n                  <jats:italic>xdh-1<\/jats:italic>\n                  ) deficiency. Remarkably,\n                  <jats:italic>xdh-1<\/jats:italic>\n                  mutant animals form rare xanthine stones, recapitulating a hallmark of human xanthinuria. To uncover genetic regulators of purine homeostasis, we performed a forward genetic screen for mutations that exacerbate xanthine stone formation in\n                  <jats:italic>xdh-1<\/jats:italic>\n                  mutants. This approach identified multiple loss-of-function alleles in a previously uncharacterized gene, which we named\n                  <jats:italic>gda-1<\/jats:italic>\n                  . We show that\n                  <jats:italic>gda-1<\/jats:italic>\n                  encodes an intestinal guanine deaminase that mediates a key enzymatic step in purine catabolism. The\n                  <jats:italic>C. elegans<\/jats:italic>\n                  genome also encodes a paralog,\n                  <jats:italic>gda-2<\/jats:italic>\n                  , which shares guanine deaminase activity but is expressed in distinct tissues. While\n                  <jats:italic>gda-2<\/jats:italic>\n                  can compensate for\n                  <jats:italic>gda-1<\/jats:italic>\n                  loss in guanine metabolism, the two genes exhibit non-redundant roles in regulating xanthine accumulation and stone formation. Interestingly, our evolutionary analyses suggest that\n                  <jats:italic>gda-2<\/jats:italic>\n                  was acquired by nematodes via horizontal gene transfer from bacteria. These findings reveal a spatially regulated purine catabolism pathway in\n                  <jats:italic>C. elegans<\/jats:italic>\n                  and suggest that acquisition of bacterial genes has shaped a core nematode metabolic network.\n                <\/jats:p>","DOI":"10.64898\/2026.04.09.715363","type":"posted-content","created":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T06:30:18Z","timestamp":1776061818000},"source":"Crossref","is-referenced-by-count":0,"title":["Paralogous guanine deaminases acquired from bacteria by horizontal gene transfer promote purine homeostasis in\n                  <i>Caenorhabditis elegans<\/i>"],"prefix":"10.64898","author":[{"given":"Sushila","family":"Bhattacharya","sequence":"first","affiliation":[{"name":"Center for Genetics and Rare Diseases Research, Sanford Research, Sioux Falls, South Dakota, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa","family":"Fischer","sequence":"additional","affiliation":[{"name":"Department of Molecular Nutrition and Biochemistry of Plants, Leibniz University Hannover, Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evrim","family":"Fer","sequence":"additional","affiliation":[{"name":"Department of Bacteriology, University of Wisconsin-Madison, Madison, WI, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Snoozy","sequence":"additional","affiliation":[{"name":"Center for Genetics and Rare Diseases Research, Sanford Research, Sioux Falls, South Dakota, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grace N.","family":"Hagedorn","sequence":"additional","affiliation":[{"name":"Center for Genetics and Rare Diseases Research, Sanford Research, Sioux Falls, South Dakota, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Herde","sequence":"additional","affiliation":[{"name":"Department of Molecular Nutrition and Biochemistry of Plants, Leibniz University Hannover, Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bet\u00fcl","family":"Ka\u00e7ar","sequence":"additional","affiliation":[{"name":"Department of Bacteriology, University of Wisconsin-Madison, Madison, WI, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claus-Peter","family":"Witte","sequence":"additional","affiliation":[{"name":"Department of Molecular Nutrition and Biochemistry of Plants, Leibniz University Hannover, Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9503-0557","authenticated-orcid":false,"given":"Kurt","family":"Warnhoff","sequence":"additional","affiliation":[{"name":"Center for Genetics and Rare Diseases Research, Sanford Research, Sioux Falls, South Dakota, USA"},{"name":"Department of Pediatrics, Sanford School of Medicine, University of South Dakota, Sioux Falls, South Dakota, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026072706214636000_2026.04.09.715363v2.1","doi-asserted-by":"publisher","DOI":"10.1186\/gb-2013-14-2-r19"},{"key":"2026072706214636000_2026.04.09.715363v2.2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2017.02.003"},{"key":"2026072706214636000_2026.04.09.715363v2.3","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2016.00173"},{"key":"2026072706214636000_2026.04.09.715363v2.4","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1121190109"},{"key":"2026072706214636000_2026.04.09.715363v2.5","doi-asserted-by":"publisher","DOI":"10.1126\/science.1187113"},{"key":"2026072706214636000_2026.04.09.715363v2.6","first-page":"e114835","article-title":"Acquired stress resilience through bacteria-to-nematode interdomain horizontal gene transfer","volume":"42","year":"2023","journal-title":"Embo j"},{"key":"2026072706214636000_2026.04.09.715363v2.7","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2022.09.041"},{"key":"2026072706214636000_2026.04.09.715363v2.8","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1008486107"},{"key":"2026072706214636000_2026.04.09.715363v2.9","doi-asserted-by":"crossref","unstructured":"Han, Z. , Sieriebriennikov, B. , Susoy, V. , Lo, W.S. , Igreja, C. , Dong, C. , Berasategui, A. , Witte, H. , and Sommer, R.J . 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