{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T16:57:16Z","timestamp":1791046636377,"version":"4.1.0"},"posted":{"date-parts":[[2026,9,29]]},"group-title":"Genetics","reference-count":45,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T00:00:00Z","timestamp":1790640000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"id":[{"id":"https:\/\/ror.org\/00hasdx88","id-type":"ROR","asserted-by":"publisher"}]},{"award":["R25HG012337"],"award-info":[{"award-number":["R25HG012337"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"name":"National Cancer Institute","award":["R01CA262556"],"award-info":[{"award-number":["R01CA262556"]}]},{"id":[{"id":"https:\/\/ror.org\/02e463172","id-type":"ROR","asserted-by":"publisher"}]},{"name":"National Institutes of Health","award":["P30 CA015704"],"award-info":[{"award-number":["P30 CA015704"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,9,29]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Buffering among paralogous genes is a well-described phenomenon in which genetic redundancy provides genetic robustness. Shared function among paralogs allows for a compensation effect when one or more paralog family genes are inactivated. Considering the role of transcriptional adaptation in influencing gene expression among highly homologous genes, we sought to identify whether transcriptional adaptation has a role in paralog buffering. We performed Perturb-seq of 110 paralog gene knockouts and assessed compensatory gene expression effects among paralogs as well as at the whole transcriptome level. This analysis identified six paralog pairs that undergo a transcriptional adaptation following CRISPR-mediated loss of one paralog in the pair. Further, we found that the upregulation of\n                  <jats:italic>TIA1<\/jats:italic>\n                  following paralog\n                  <jats:italic>TIAL1<\/jats:italic>\n                  loss requires nonsense-mediated decay, and active nuclear import via the importin IPO8. These data provide a comprehensive evaluation of transcriptional adaptation and show that transcriptional adaptation is recurrent but not pervasive among paralogous human genes.\n                <\/jats:p>","DOI":"10.64898\/2026.09.24.754217","type":"posted-content","created":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T06:25:12Z","timestamp":1790749512000},"source":"Crossref","is-referenced-by-count":0,"title":["Transcriptional adaptation influences buffering among essential paralog gene families"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4958-1080","authenticated-orcid":false,"given":"Siobhan","family":"O\u2019Brien","sequence":"first","affiliation":[{"name":"Human Biology Division, Fred Hutchinson Cancer Center, Seattle, WA 98109, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-1288-7067","authenticated-orcid":false,"given":"Marissa H.","family":"Fujimoto","sequence":"additional","affiliation":[{"name":"Human Biology Division, Fred Hutchinson Cancer Center, Seattle, WA 98109, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy R.","family":"Lowe","sequence":"additional","affiliation":[{"name":"Human Biology Division, Fred Hutchinson Cancer Center, Seattle, WA 98109, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6538-2658","authenticated-orcid":false,"given":"Alice H.","family":"Berger","sequence":"additional","affiliation":[{"name":"Human Biology Division, Fred Hutchinson Cancer Center, Seattle, WA 98109, USA"},{"name":"Herbold Computational Biology Program, Public Health Sciences Division, Fred Hutchinson Cancer Center, Seattle, WA 98109, USA"},{"name":"Department of Genome Sciences, University of Washington, Seattle, WA 98195, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026100309450523000_2026.09.24.754217v1.1","doi-asserted-by":"publisher","DOI":"10.1038\/nature01198"},{"key":"2026100309450523000_2026.09.24.754217v1.2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1008466"},{"key":"2026100309450523000_2026.09.24.754217v1.3","doi-asserted-by":"publisher","DOI":"10.1126\/science.aac7041"},{"key":"2026100309450523000_2026.09.24.754217v1.4","doi-asserted-by":"crossref","unstructured":"Parrish, P. 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