{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T03:39:20Z","timestamp":1776051560070,"version":"3.50.1"},"posted":{"date-parts":[[2023,3,15]]},"group-title":"Evolutionary Biology","reference-count":83,"publisher":"openRxiv","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2023,6,27]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Although previously thought to be unlikely, recent studies have shown that\n                  <jats:italic>de novo<\/jats:italic>\n                  gene origination from previously non-genic sequences is a relatively common mechanism for gene innovation in many species and taxa. These young genes provide a unique set of candidates to study the structural and functional origination of proteins. However, our understanding of their protein structures and how these structures originate and evolve are still limited, due to a lack of systematic studies. Here, we combined high-quality base-level whole genome alignments, bioinformatic analysis, and computational structure modeling to study the origination, evolution, and protein structure of lineage-specific\n                  <jats:italic>de novo<\/jats:italic>\n                  genes. We identified 555\n                  <jats:italic>de novo<\/jats:italic>\n                  gene candidates in\n                  <jats:italic>D. melanogaster<\/jats:italic>\n                  that originated within the\n                  <jats:italic>Drosophilinae<\/jats:italic>\n                  lineage. We found a gradual shift in sequence composition, evolutionary rates, and expression patterns with their gene ages, which indicates possible gradual shifts or adaptations of their functions. Surprisingly, we found little overall protein structural changes for\n                  <jats:italic>de novo<\/jats:italic>\n                  genes in the\n                  <jats:italic>Drosophilinae<\/jats:italic>\n                  lineage. Using Alphafold2, ESMFold, and molecular dynamics, we identified a number of\n                  <jats:italic>de novo<\/jats:italic>\n                  gene candidates with protein products that are potentially well-folded, many of which are more likely to contain transmembrane and signal proteins compared to other annotated protein-coding genes. Using ancestral sequence reconstruction, we found that most potentially well-folded proteins are often born folded. Interestingly, we observed one case where disordered ancestral proteins become ordered within a relatively short evolutionary time. Single-cell RNA-seq analysis in testis showed that although most\n                  <jats:italic>de novo<\/jats:italic>\n                  genes are enriched in spermatocytes, several young\n                  <jats:italic>de novo<\/jats:italic>\n                  genes are biased in the early spermatogenesis stage, indicating potentially important but less emphasized roles of early germline cells in the\n                  <jats:italic>de novo<\/jats:italic>\n                  gene origination in testis. This study provides a systematic overview of the origin, evolution, and structural changes of\n                  <jats:italic>Drosophilinae<\/jats:italic>\n                  -specific\n                  <jats:italic>de novo<\/jats:italic>\n                  genes.\n                <\/jats:p>","DOI":"10.1101\/2023.03.13.532420","type":"posted-content","created":{"date-parts":[[2023,3,15]],"date-time":"2023-03-15T10:31:12Z","timestamp":1678876272000},"source":"Crossref","is-referenced-by-count":11,"title":["The origin and structural evolution of\n                  <i>de novo<\/i>\n                  genes in\n                  <i>Drosophila<\/i>"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2855-2299","authenticated-orcid":false,"given":"Junhui","family":"Peng","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6776-1996","authenticated-orcid":false,"given":"Li","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2023070108201387000_2023.03.13.532420v2.1","first-page":"19","article-title":"Gromacs: High performance molecular simulations through multi-level parallelism from laptops to supercomputers","volume":"1\u20132","year":"2015","journal-title":"SoftwareX"},{"key":"2023070108201387000_2023.03.13.532420v2.2","doi-asserted-by":"publisher","DOI":"10.1534\/genetics.113.152256"},{"key":"2023070108201387000_2023.03.13.532420v2.3","doi-asserted-by":"publisher","DOI":"10.1038\/s41587-019-0036-z"},{"key":"2023070108201387000_2023.03.13.532420v2.4","doi-asserted-by":"publisher","DOI":"10.1006\/jmbi.1990.9999"},{"key":"2023070108201387000_2023.03.13.532420v2.5","doi-asserted-by":"crossref","unstructured":"An, N. A. , Zhang, J. , Mo, F. , Luan, X. , Tian, L. , Shen, Q. S. , Li, X. , Li, C. , Zhou, F. , Zhang, B. , Ji, M. , Qi, J. , Zhou, W.-Z. , Ding, W. , Chen, J.-Y. , Yu, J. , Zhang, L. , Shu, S. , Hu, B. , & Li, C.-Y. (2023). De novo genes with an lncRNA origin encode unique human brain developmental functionality. Nature Ecology & Evolution. https:\/\/doi.org\/10.1038\/s41559-022-01925-6","DOI":"10.1038\/s41559-022-01925-6"},{"key":"2023070108201387000_2023.03.13.532420v2.6","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2871-y"},{"key":"2023070108201387000_2023.03.13.532420v2.7","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0213712"},{"key":"2023070108201387000_2023.03.13.532420v2.8","doi-asserted-by":"publisher","DOI":"10.1126\/science.abj8754"},{"key":"2023070108201387000_2023.03.13.532420v2.9","doi-asserted-by":"crossref","unstructured":"Bateman, A. , Martin, M.-J. , Orchard, S. , Magrane, M. , Ahmad, S. , Alpi, E. , Bowler-Barnett, E. 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