ArticleCell reports2022
De novo birth of functional microproteins in the human lineage.
Article in Cell reports, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 67 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
67 citing papers in PubMed, 103 citations in OpenAlex.
- DetectNAR genomics and bioinformatics · 2026Article
- Review
- Mapping the functional dark proteome in cancer.Nature reviews. Cancer · 2026Review
- Molting in Pancrustacea Is Characterized by Both Deeply Conserved and Recently Evolved Gene Modules.Genome biology and evolution · 2026Article
- Identification of unannotated microproteins involved in endothelial cell homeostasis, dysfunction, and vascular disease.Cardiovascular research · 2026Article
- STREMI: a dual-function upstream ORF-encoded regulator of mitochondrial cristae architecture.EMBO reports · 2026Article
- Emergence and evolution of chimeric pseudogenes (φgenes) contribute to genetic and functional diversity of the human genome.Nucleic acids research · 2026Article
- Microproteins in Human Physiology and Pathology.Biochemistry · 2026Review
- An expanded reference catalog of translated open reading frames for biomedical research.Nucleic acids research · 2026Article
- Degradation Determinants Are Abundant in Human Noncanonical Proteins and Minor Annotated Isoforms.Genome biology and evolution · 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
- Structure and Disorder Predictions of Microproteins: Usage, Applications, and Pitfalls.Methods in molecular biology (Clifton, N.J.) · 2026Article
- The 'non-conventional' peptidome: A new layer in plant regulatory mechanisms.Plant communications · 2025Review
- Decoding the Cryptic Proteome Between Antigens and Novel Functional Proteins.European journal of immunology · 2025Review
- An integrative multitiered computational analysis for better understanding the structure and function of 85 miniproteins.NAR genomics and bioinformatics · 2025Article
- Multiple human enhancer RNAs contain long translated open reading frames.Genes & development · 2025Article
- Orphan and de novo Genes in Fungi and Animals: Identification, Origins and Functions.Genome biology and evolution · 2025Review
- De Novo Genes: Current Status and Future Goals.Genome biology and evolution · 2025Article
- De novo origin of numerous microproteins in enterobacteria.Nucleic acids research · 2025Article
- Chasing the Ghost Proteome in the Dark Matter.Molecular & cellular proteomics : MCP · 2025Review
7 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Small open reading frames (sORFs) can encode functional "microproteins" that perform crucial biological tasks. However, their size makes them less amenable to genomic analysis, and their origins and conservation are poorly understood. Given their short length, it is plausible that some of these functional microproteins have recently originated entirely de novo from noncoding sequences. Here we sought to identify such cases in the human lineage by reconstructing the evolutionary origins of human microproteins previously found to have measurable, statistically significant fitness effects. By tracing the formation of each ORF and its transcriptional activation, we show that novel microproteins with significant phenotypic effects have emerged de novo throughout animal evolution, including two after the human-chimpanzee split. Notably, traditional methods for assessing coding potential would miss most of these cases. This evidence demonstrates that the functional potential intrinsic to sORFs can be relatively rapidly and frequently realized through de novo gene emergence.
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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.