Proto-genes and de novo gene birth
Open accessAbstract
Novel protein-coding genes can arise either through re-organization of pre-existing genes or de novo. Processes involving re-organization of pre-existing genes, notably after gene duplication, have been extensively described. In contrast, de novo gene birth remains poorly understood, mainly because translation of sequences devoid of genes, or 'non-genic' sequences, is expected to produce insignificant polypeptides rather than proteins with specific biological functions. Here we formalize an evolutionary model according to which functional genes evolve de novo through transitory proto-genes generated by widespread translational activity in non-genic sequences. Testing this model at the genome scale in Saccharomyces cerevisiae, we detect translation of hundreds of short species-specific open reading frames (ORFs) located in non-genic sequences. These translation events seem to provide adaptive potential, as suggested by their differential regulation upon stress and by signatures of retention by natural selection. In line with our model, we establish that S. cerevisiae ORFs can be placed within an evolutionary continuum ranging from non-genic sequences to genes. We identify ~1,900 candidate proto-genes among S. cerevisiae ORFs and find that de novo gene birth from such a reservoir may be more prevalent than sporadic gene duplication. Our work illustrates that evolution exploits seemingly dispensable sequences to generate adaptive functional innovation.
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De novo gene birth represents a radical innovation because it recruits entirely novel sequences into coding function, unlike duplication or shuffling which rely on pre-existing genes or fragments.
“Unlike other mechanisms such as duplication or shuffling, which rely on pre-existing genes or gene fragments, de novo gene formation represents a radical innovation, as it involves the recruitment of entirely novel sequences into coding function [26].”
From Origin and Evolution of Genes in Eukaryotes: Mechanisms, Dynamics, and Functional Implications (2025) · cites this paper as [26]
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“Unlike other mechanisms such as duplication or shuffling, which rely on pre-existing genes or gene fragments, de novo gene formation represents a radical innovation, as it involves the recruitment of entirely novel sequences into coding function [26].”
- Authors
- Carvunis, A.-R., Rolland, T., Wapinski, I., Calderwood, M. A., Yildirim, M. A., Simonis, N., Charloteaux, B., Hidalgo, C. A., Barbette, J., Santhanam, B., Brar, G. A., Weissman, J. S., Regev, A., Thierry-Mieg, N., Cusick, M. E., & Vidal, M.
- Affiliations
- Dana-Farber Cancer Institute (US)
- Harvard University (US)
- MIT Media Lab (US)
- QB3 (US)
- Broad Institute (US)
- Corresponding author
- Vidal, Marc
- ORCID
- Venue
- Nature
- Published
- 2012-06-24
- Volume
- 487
- Issue
- 7407
- Pages
- 370-374
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC3401362
- OpenAlex
- W2127673162
- Cited by
- 669
- References
- 31
- Citations by year
- 2026: 42 · 2025: 49 · 2024: 58 · 2023: 60 · 2022: 61 · 2021: 55 · 2020: 39 · 2019: 48 · 2018: 42 · 2017: 48 · 2016: 32 · 2015: 38 · 2014: 42 · 2013: 45 · 2012: 9
- FWCI
- 48.86
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- HAL (submittedVersion)
- Dépôt institutionnel de l'Université libre de Bruxelles (Université Libre de Bruxelles) (submittedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Open Repository and Bibliography (University of Liège) (submittedVersion)
- Funders
- Howard Hughes Medical Institute
- National Human Genome Research Institute (R01HG006061)
- Topics
- Life Sciences › Agricultural and Biological Sciences › Plant Science › Chromosomal and Genetic Variations
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Evolution and Genetic Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Phylogenetic Studies
- Keywords
- de novo gene birth, open reading frames, Saccharomyces cerevisiae, stress response, natural selection, gene evolution, gene duplication
- MeSH terms
- Base Sequence, Genes, Fungal, Molecular Sequence Data, Phylogeny, Saccharomyces, Saccharomyces cerevisiae, Protein Biosynthesis, Genetic Variation, Open Reading Frames, Sequence Alignment, Conserved Sequence, Evolution, Molecular
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