{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T13:45:21Z","timestamp":1784295921756,"version":"3.55.0"},"reference-count":66,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2023,10,9]],"date-time":"2023-10-09T00:00:00Z","timestamp":1696809600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"FIR 2021"},{"name":"Universit\u00e0 Cattolica del Sacro Cuore (Rome, Italy)"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Saliva houses over 2000 proteins and peptides with poorly clarified functions, including proline-rich proteins, statherin, P-B peptides, histatins, cystatins, and amylases. Their genes are poorly conserved across related species, reflecting an evolutionary adaptation. We searched the nucleotide substitutions fixed in these salivary proteins\u2019 gene loci in modern humans compared with ancient hominins. We mapped 3472 sequence variants\/nucleotide substitutions in coding, noncoding, and 5\u2032-3\u2032 untranslated regions. Despite most of the detected variations being within noncoding regions, the frequency of coding variations was far higher than the general rate found throughout the genome. Among the various missense substitutions, specific substitutions detected in PRB1 and PRB2 genes were responsible for the introduction\/abrogation of consensus sequences recognized by convertase enzymes that cleave the protein precursors. Overall, these changes that occurred during the recent human evolution might have generated novel functional features and\/or different expression ratios among the various components of the salivary proteome. This may have influenced the homeostasis of the oral cavity environment, possibly conditioning the eating habits of modern humans. However, fixed nucleotide changes in modern humans represented only 7.3% of all the substitutions reported in this study, and no signs of evolutionary pressure or adaptative introgression from archaic hominins were found on the tested genes.<\/jats:p>","DOI":"10.3390\/ijms241915010","type":"journal-article","created":{"date-parts":[[2023,10,9]],"date-time":"2023-10-09T07:37:50Z","timestamp":1696837070000},"page":"15010","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["A Catalog of Coding Sequence Variations in Salivary Proteins\u2019 Genes Occurring during Recent Human Evolution"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5723-2169","authenticated-orcid":false,"given":"Lorena","family":"Di Pietro","sequence":"first","affiliation":[{"name":"Dipartimento Scienze della Vita e Sanit\u00e0 Pubblica, Universit\u00e0 Cattolica del Sacro Cuore, 00168 Rome, Italy"},{"name":"Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3239-4775","authenticated-orcid":false,"given":"Mozhgan","family":"Boroumand","sequence":"additional","affiliation":[{"name":"Laboratorio di Proteomica, Centro Europeo di Ricerca sul Cervello, IRCCS Fondazione Santa Lucia, 00179 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3092-4936","authenticated-orcid":false,"given":"Wanda","family":"Lattanzi","sequence":"additional","affiliation":[{"name":"Dipartimento Scienze della Vita e Sanit\u00e0 Pubblica, Universit\u00e0 Cattolica del Sacro Cuore, 00168 Rome, Italy"},{"name":"Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2880-9915","authenticated-orcid":false,"given":"Barbara","family":"Manconi","sequence":"additional","affiliation":[{"name":"Dipartimento di Scienze della Vita e Dell\u2019ambiente, Universit\u00e0 di Cagliari, 09042 Monserrato, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martina","family":"Salvati","sequence":"additional","affiliation":[{"name":"Dipartimento Scienze della Vita e Sanit\u00e0 Pubblica, Universit\u00e0 Cattolica del Sacro Cuore, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7535-9825","authenticated-orcid":false,"given":"Tiziana","family":"Cabras","sequence":"additional","affiliation":[{"name":"Dipartimento di Scienze della Vita e Dell\u2019ambiente, Universit\u00e0 di Cagliari, 09042 Monserrato, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandra","family":"Olianas","sequence":"additional","affiliation":[{"name":"Dipartimento di Scienze della Vita e Dell\u2019ambiente, Universit\u00e0 di Cagliari, 09042 Monserrato, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Flore","sequence":"additional","affiliation":[{"name":"Dipartimento di Scienze della Vita e Dell\u2019ambiente, Universit\u00e0 di Cagliari, 09042 Monserrato, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1881-856X","authenticated-orcid":false,"given":"Simone","family":"Serrao","sequence":"additional","affiliation":[{"name":"Department of Medicine and Surgery, Proteomics and Metabolomics Unit, University of Milano-Bicocca, 20854 Vedano al Lambro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carla M.","family":"Cal\u00f2","sequence":"additional","affiliation":[{"name":"Dipartimento di Scienze della Vita e Dell\u2019ambiente, Universit\u00e0 di Cagliari, 09042 Monserrato, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7912-162X","authenticated-orcid":false,"given":"Paolo","family":"Francalacci","sequence":"additional","affiliation":[{"name":"Dipartimento di Scienze della Vita e Dell\u2019ambiente, Universit\u00e0 di Cagliari, 09042 Monserrato, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5211-6430","authenticated-orcid":false,"given":"Ornella","family":"Parolini","sequence":"additional","affiliation":[{"name":"Dipartimento Scienze della Vita e Sanit\u00e0 Pubblica, Universit\u00e0 Cattolica del Sacro Cuore, 00168 Rome, Italy"},{"name":"Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0959-7259","authenticated-orcid":false,"given":"Massimo","family":"Castagnola","sequence":"additional","affiliation":[{"name":"Laboratorio di Proteomica, Centro Europeo di Ricerca sul Cervello, IRCCS Fondazione Santa Lucia, 00179 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,10,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"563","DOI":"10.4155\/bio.13.349","article-title":"Top-down analytical platforms for the characterization of the human salivary proteome","volume":"6","author":"Cabras","year":"2014","journal-title":"Bioanalysis"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"5590","DOI":"10.1021\/pr900675w","article-title":"A Dynamic Range Compression and Three-Dimensional Peptide Fractionation Analysis Platform Expands Proteome Coverage and the Diagnostic Potential of Whole Saliva","volume":"8","author":"Bandhakavi","year":"2009","journal-title":"J. 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