ArticleNature2012
Proto-genes and de novo gene birth.
Article in Nature, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 407 papers.
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Who cites it
407 citing papers in PubMed, 694 citations in OpenAlex.
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- Imported, not invented, genes prevail amongProceedings of the National Academy of Sciences of the United States of America · 2026Article
- Emergence and Tandem Repeat-Mediated Elongation of a Translated De Novo Open Reading Frame in Human Oncogenic RNA Gene VPS9D1-AS1 (MYU).Genome biology and evolution · 2026Article
- Systematic discovery of retina-enriched Rik genes identifies 1190005I06Rik as a novel modulator of visual signalling.Journal of translational medicine · 2026Article
- Impact of GC content on de novo gene birth.Nature communications · 2026Article
- Novel genes arise from genomic deletions across the bacterial tree of life.bioRxiv : the preprint server for biology · 2026Article
- Article
347 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
16 authors at 7 institutions in 3 countries.
Funding
Abstract
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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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.