{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T01:56:12Z","timestamp":1790560572913,"version":"4.1.0"},"reference-count":30,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T00:00:00Z","timestamp":1789689600000},"content-version":"vor","delay-in-days":17,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100008982","name":"National Science Foundation","doi-asserted-by":"publisher","award":["MCB-2129845"],"award-info":[{"award-number":["MCB-2129845"]}],"id":[{"id":"10.13039\/501100008982","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000038","name":"Natural Sciences and Engineering Research Council Discovery","doi-asserted-by":"publisher","award":["RGPIN-2025-04591"],"award-info":[{"award-number":["RGPIN-2025-04591"]}],"id":[{"id":"10.13039\/501100000038","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,9,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Seminal fluid proteins (SFPs)-encoding genes are rapidly evolving at the sequence level and often considered prone to frequent phylogenetic turnover. One mechanism underlying such rapid turnover is the lineage-restricted origin of new SFP genes, which results in a complement of phylogenetically young genes. Recent advances in genome resources and comparative genomics now enable more comprehensive cross-taxa analyses, providing improved estimates of the timing of gene origin during evolution. Using these resources alongside proteomic data from human seminal plasma, we traced the evolutionary origins of 646 putative human SFP genes. We find that most SFPs trace back to the bony vertebrate (Euteleostomi) radiation. These ancient SFP genes are more pleiotropic than younger ones, which are enriched in immunity-related functions and regulate proteolytic activity, particularly peptidase inhibitors. Together, these results underscore that the human proteome components of the seminal plasma originated early during vertebrate evolution, providing insights into the history of reproductive biology in deuterostomes.<\/jats:p>","DOI":"10.1093\/gbe\/evag236","type":"journal-article","created":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T19:20:01Z","timestamp":1789672801000},"source":"Crossref","is-referenced-by-count":0,"title":["Early Origin of the Human Seminal Plasma Proteome During Vertebrate Evolution"],"prefix":"10.1093","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3585-3129","authenticated-orcid":false,"given":"Jose M","family":"Ranz","sequence":"first","affiliation":[{"name":"Department of Ecology and Evolutionary Biology, University of California Irvine , Irvine ,","place":["USA"]},{"name":"Department of Systems Biology, University of California Irvine , Irvine ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9122-5621","authenticated-orcid":false,"given":"Alberto","family":"Civetta","sequence":"additional","affiliation":[{"name":"Department of Biology, University of Winnipeg , Winnipeg ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,9,18]]},"reference":[{"key":"2026092721215549800_evag236-B1","doi-asserted-by":"publisher","first-page":"411","DOI":"10.1093\/biolre\/ioaa075","article-title":"Mechanism of semen liquefaction and its potential for a novel non-hormonal contraceptiondagger","volume":"103","author":"Anamthathmakula","year":"2020","journal-title":"Biol Reprod"},{"key":"2026092721215549800_evag236-B2","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1146\/annurev-ento-120709-144823","article-title":"Insect seminal fluid proteins: identification and function","volume":"56","author":"Avila","year":"2011","journal-title":"Annu Rev Entomol"},{"key":"2026092721215549800_evag236-B3","doi-asserted-by":"publisher","first-page":"941","DOI":"10.1021\/pr100745u","article-title":"Proteomic analysis of seminal plasma from normal volunteers and post-vasectomy patients identifies over 2000 proteins and candidate biomarkers of the urogenital system","volume":"10","author":"Batruch","year":"2011","journal-title":"J Proteome Res"},{"key":"2026092721215549800_evag236-B4","doi-asserted-by":"publisher","first-page":"289","DOI":"10.1111\/j.2517-6161.1995.tb02031.x","article-title":"Controlling the false discovery rate\u2014a practical and powerful approach to multiple testing","volume":"57","author":"Benjamini","year":"1995","journal-title":"J R Stat Soc Ser B-Methodol"},{"key":"2026092721215549800_evag236-B5","doi-asserted-by":"publisher","first-page":"379","DOI":"10.1101\/gr.279498.124","article-title":"Evolutionarily new genes in humans with disease phenotypes reveal functional enrichment patterns shaped by adaptive innovation and sexual selection","volume":"35","author":"Chen","year":"2025","journal-title":"Genome Res"},{"key":"2026092721215549800_evag236-B6","doi-asserted-by":"publisher","first-page":"e35","DOI":"10.1371\/journal.pgen.0010035","article-title":"Pervasive adaptive evolution in primate seminal proteins","volume":"1","author":"Clark","year":"2005","journal-title":"PLoS Genet."},{"key":"2026092721215549800_evag236-B7","doi-asserted-by":"publisher","first-page":"213","DOI":"10.3109\/01485019408987788","article-title":"Alteration of semen characteristics and regulatory factors in human semen with bacterial infection","volume":"32","author":"Gopalkrishnan","year":"1994","journal-title":"Arch Androl"},{"key":"2026092721215549800_evag236-B8","doi-asserted-by":"publisher","first-page":"316","DOI":"10.1186\/1471-2148-10-316","article-title":"Human functional genetic studies are biased against the medically most relevant primate-specific genes","volume":"10","author":"Hao","year":"2010","journal-title":"BMC Evol Biol"},{"key":"2026092721215549800_evag236-B9","doi-asserted-by":"publisher","first-page":"msac174","DOI":"10.1093\/molbev\/msac174","article-title":"TimeTree 5: an expanded resource for species divergence times","volume":"39","author":"Kumar","year":"2022","journal-title":"Mol Biol Evol"},{"key":"2026092721215549800_evag236-B10","doi-asserted-by":"publisher","first-page":"80","DOI":"10.1002\/mrd.22130","article-title":"Identification and function of proteolysis regulators in seminal fluid","volume":"80","author":"Laflamme","year":"2013","journal-title":"Mol Reprod Dev"},{"key":"2026092721215549800_evag236-B11","doi-asserted-by":"publisher","first-page":"281","DOI":"10.1172\/JCI113070","article-title":"Seminal vesicle-secreted proteins and their reactions during gelation and liquefaction of human semen","volume":"80","author":"Lilja","year":"1987","journal-title":"J Clin Invest"},{"key":"2026092721215549800_evag236-B12","doi-asserted-by":"publisher","first-page":"142","DOI":"10.1002\/bies.201400117","article-title":"On a matter of seminal importance","volume":"37","author":"McGraw","year":"2015","journal-title":"Bioessays"},{"key":"2026092721215549800_evag236-B13","doi-asserted-by":"publisher","first-page":"1497","DOI":"10.21037\/tau-23-130","article-title":"Proteomic approach towards identification of seminal fluid biomarkers from individuals with severe oligozoospermia, cryptozoospermia and non-obstructive azoospermia: a pilot study","volume":"12","author":"Nowicka-Bauer","year":"2023","journal-title":"Transl Androl Urol"},{"key":"2026092721215549800_evag236-B14","first-page":"465","article-title":"Ultrastructural study of the specific granule of the human eosinophil","volume":"13","author":"Okuda","year":"1981","journal-title":"J Submicrosc Cytol"},{"key":"2026092721215549800_evag236-B15","doi-asserted-by":"publisher","first-page":"e13989","DOI":"10.1111\/and.13989","article-title":"The current perspective on genetic and epigenetic factors in sperm maturation in the epididymis","volume":"53","author":"Ozkocer","year":"2021","journal-title":"Andrologia"},{"key":"2026092721215549800_evag236-B16","doi-asserted-by":"publisher","first-page":"3313","DOI":"10.18632\/aging.202648","article-title":"Ageing transcriptome meta-analysis reveals similarities and differences between key mammalian tissues","volume":"13","author":"Palmer","year":"2021","journal-title":"Aging (Albany NY)"},{"key":"2026092721215549800_evag236-B17","doi-asserted-by":"publisher","first-page":"3551","DOI":"10.1002\/(SICI)1522-2683(19991201)20:18&lt;3551::AID-ELPS3551&gt;3.0.CO;2-2","article-title":"Probability-based protein identification by searching sequence databases using mass spectrometry data","volume":"20","author":"Perkins","year":"1999","journal-title":"Electrophoresis"},{"key":"2026092721215549800_evag236-B18","doi-asserted-by":"publisher","first-page":"R40","DOI":"10.1186\/gb-2006-7-5-r40","article-title":"Large-scale and high-confidence proteomic analysis of human seminal plasma","volume":"7","author":"Pilch","year":"2006","journal-title":"Genome Biol"},{"key":"2026092721215549800_evag236-B19","doi-asserted-by":"publisher","first-page":"207","DOI":"10.1093\/molbev\/msm242","article-title":"Sexual selection and the adaptive evolution of mammalian ejaculate proteins","volume":"25","author":"Ramm","year":"2008","journal-title":"Mol Biol Evol"},{"key":"2026092721215549800_evag236-B20","doi-asserted-by":"publisher","first-page":"e2505490122","DOI":"10.1073\/pnas.2505490122","article-title":"Gene age shapes functional and evolutionary properties of the Drosophila seminal fluid proteome","volume":"122","author":"Ranz","year":"2025","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2026092721215549800_evag236-B21","volume-title":"R: a language and environment for statistical computing","author":"R Development Core Team","year":"2016"},{"key":"2026092721215549800_evag236-B22","doi-asserted-by":"publisher","first-page":"1735","DOI":"10.1073\/pnas.95.4.1735","article-title":"Prostate stem cell antigen: a cell surface marker overexpressed in prostate cancer","volume":"95","author":"Reiter","year":"1998","journal-title":"Proc Natl Acad Sci U S A."},{"key":"2026092721215549800_evag236-B23","doi-asserted-by":"publisher","DOI":"10.17912\/micropub.biology.000811","article-title":"rrvgo: a bioconductor package for interpreting lists of gene ontology terms","volume":"2023","author":"Sayols","journal-title":"MicroPubl Biol"},{"key":"2026092721215549800_evag236-B24","doi-asserted-by":"publisher","first-page":"1077","DOI":"10.1152\/physrev.00013.2018","article-title":"The female response to seminal fluid","volume":"100","author":"Schjenken","year":"2020","journal-title":"Physiol Rev"},{"key":"2026092721215549800_evag236-B25","doi-asserted-by":"publisher","first-page":"682","DOI":"10.1101\/gr.238733.118","article-title":"GenTree, an integrated resource for analyzing the evolution and function of primate-specific coding genes","volume":"29","author":"Shao","year":"2019","journal-title":"Genome Res"},{"key":"2026092721215549800_evag236-B26","doi-asserted-by":"publisher","first-page":"W216","DOI":"10.1093\/nar\/gkac194","article-title":"DAVID: a web server for functional enrichment analysis and functional annotation of gene lists (2021 update)","volume":"50","author":"Sherman","year":"2022","journal-title":"Nucleic Acids Res"},{"key":"2026092721215549800_evag236-B27","doi-asserted-by":"publisher","first-page":"137","DOI":"10.1038\/nrg733","article-title":"The rapid evolution of reproductive proteins","volume":"3","author":"Swanson","year":"2002","journal-title":"Nat Rev Genet"},{"key":"2026092721215549800_evag236-B28","doi-asserted-by":"publisher","first-page":"187","DOI":"10.1002\/pros.10178","article-title":"Down-regulated expression of prostasin in high-grade or hormone-refractory human prostate cancers","volume":"54","author":"Takahashi","year":"2003","journal-title":"Prostate"},{"key":"2026092721215549800_evag236-B29","doi-asserted-by":"publisher","first-page":"650","DOI":"10.1093\/bioinformatics\/bti042","article-title":"Genome-wide midrange transcription profiles reveal expression level relationships in human tissue specification","volume":"21","author":"Yanai","year":"2005","journal-title":"Bioinformatics"},{"key":"2026092721215549800_evag236-B30","doi-asserted-by":"publisher","first-page":"3855","DOI":"10.1038\/s41467-021-24145-1","article-title":"Direct activation of the proton channel by albumin leads to human sperm capacitation and sustained release of inflammatory mediators by neutrophils","volume":"12","author":"Zhao","year":"2021","journal-title":"Nat Commun"}],"container-title":["Genome Biology and Evolution"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/gbe\/advance-article-pdf\/doi\/10.1093\/gbe\/evag236\/71208268\/evag236.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/gbe\/article-pdf\/18\/9\/evag236\/71208268\/evag236.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/gbe\/article-pdf\/18\/9\/evag236\/71208268\/evag236.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T01:22:12Z","timestamp":1790558532000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/gbe\/article\/doi\/10.1093\/gbe\/evag236\/8815037"}},"subtitle":[],"editor":[{"given":"Xiaoshu","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2026,9]]},"references-count":30,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2026,9,2]]}},"URL":"https:\/\/doi.org\/10.1093\/gbe\/evag236","relation":{},"ISSN":["1759-6653"],"issn-type":[{"value":"1759-6653","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2026,9]]},"published":{"date-parts":[[2026,9]]},"article-number":"evag236"}}