{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T03:26:23Z","timestamp":1793157983941,"version":"4.5.0"},"update-to":[{"DOI":"10.1371\/journal.pgen.1012071","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T00:00:00Z","timestamp":1791504000000}}],"reference-count":77,"publisher":"Public Library of Science (PLoS)","issue":"9","license":[{"start":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T00:00:00Z","timestamp":1790553600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["DK303003784"],"award-info":[{"award-number":["DK303003784"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosgenetics.org"],"crossmark-restriction":false},"short-container-title":["PLoS Genet"],"abstract":"<jats:p>\n                    Lysosome-rich enterocytes (LREs) are a specialized population of intestinal cells that mediate the uptake and absorption of dietary proteins in fish and neonatal mammals. Loss of LRE function causes inhibited growth and poor survival due to protein malnutrition. Previously, we reported that in zebrafish loss of Plasmolipin (pllp), an endosomal membrane protein highly expressed in LREs, impairs LRE differentiation and dietary protein absorption, resulting in marked reduction in survival rates. Raising\n                    <jats:italic>pllp<\/jats:italic>\n                    homozygous mutants surviving to adulthood and in-crossing them for multiple generations resulted in a recovery of survival and growth, even when fed a low protein diet. To uncover mechanisms underlying this phenomenon, we compared the older adapted\n                    <jats:italic>pllp<\/jats:italic>\n                    allele with genetically related wild type (WT) fish and a newly generated\n                    <jats:italic>pllp<\/jats:italic>\n                    mutant allele. Using transcriptome profiling and quantitative protein absorption assays, we found that the adapted\n                    <jats:italic>pllp<\/jats:italic>\n                    mutants exhibit upregulation of LRE endocytic components associated with a capacity for protein absorption that exceeds that of WT. This hyperactivation of LRE endocytic and absorptive activity is accompanied by transcriptional regulation of immune genes that may contribute to the enhanced survival of\n                    <jats:italic>pllp<\/jats:italic>\n                    mutants in the face of increased exposure to environmental antigens. Genetic analyses indicate that these divergent phenotypes emerge gradually over generations and can recur in an independently generated\n                    <jats:italic>pllp<\/jats:italic>\n                    allele upon inbreeding and natural selection. Overall, our study illustrates that genome-wide transcriptional changes are associated with stable improvements in intestinal function and organismal survival in response to protein malnutrition.\n                  <\/jats:p>","DOI":"10.1371\/journal.pgen.1012071","type":"journal-article","created":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T17:50:56Z","timestamp":1790617856000},"page":"e1012071","update-policy":"https:\/\/doi.org\/10.1371\/journal.pgen.corrections_policy","source":"Crossref","is-referenced-by-count":1,"title":["Genome wide transcriptional changes underlie gradual and recurrent adaptation to protein malnutrition in zebrafish"],"prefix":"10.1371","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4112-4187","authenticated-orcid":true,"given":"Siyao","family":"Wang","sequence":"first","affiliation":[{"name":"Duke University","place":["Durham, North Carolina, United States of America"],"department":["Department of Cell 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