ArticleJournal of virology2009
Overlapping genes produce proteins with unusual sequence properties and offer insight into de novo protein creation.
Article in Journal of virology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 107 papers, 1 of them a synthesis that pooled it.
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Who cites it
107 citing papers in PubMed, 1 synthesis or guideline pooled it, 186 citations in OpenAlex.
- Pooled it
- Metagenomic Analysis Reveals Viral Diversity in Phlebotomine Sand Flies from Caribbean Region in Colombia.Microorganisms · 2026Article
- The Gene Encoding the Antisense Protein ASP of HIV-1: Origin, Distribution and Maintenance.Viruses · 2026Review
- Systematic Detection of Alternative Open Reading Frames (altORFs) in Cancer Driver Genes.Journal of molecular evolution · 2026Article
- De Novo Gene Emergence: Summary, Classification, and Challenges of Current Methods.Genome biology and evolution · 2025Review
- Design of overlapping genes using deep generative models of protein sequences.bioRxiv : the preprint server for biology · 2025Article
- Creation of the HIV-1 antisense geneMicrobiology spectrum · 2024Article
- Overlaps Between CDS Regions of Protein-Coding Genes in the Human Genome: A Case Study on the NR1D1-THRA Gene Pair.Journal of molecular evolution · 2023Article
- Alternative Reading Frames are an Underappreciated Source of Protein Sequence Novelty.Journal of molecular evolution · 2023Review
- A small protein coded within the mitochondrial canonical gene nd4 regulates mitochondrial bioenergetics.BMC biology · 2023Article
- Three Novel Antisense Overlapping Genes in E. coli O157:H7 EDL933.Microbiology spectrum · 2023Article
- Viral Complexity.Biomolecules · 2022Review
- Spacer Domain in Hepatitis B Virus Polymerase: Plugging a Hole or Performing a Role?Journal of virology · 2022Review
- Article
- Gene Overlapping as a Modulator ofMicroorganisms · 2022Article
- Computational methods for inferring location and genealogy of overlapping genes in virus genomes: approaches and applications.Current opinion in virology · 2022Review
- Using networks to analyze and visualize the distribution of overlapping genes in virus genomes.PLoS pathogens · 2022Article
- Article
- Article
- Hundreds of Out-of-Frame Remodeled Gene Families in the Escherichia coli Pangenome.Molecular biology and evolution · 2022Article
47 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
5 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
It is widely assumed that new proteins are created by duplication, fusion, or fission of existing coding sequences. Another mechanism of protein birth is provided by overlapping genes. They are created de novo by mutations within a coding sequence that lead to the expression of a novel protein in another reading frame, a process called "overprinting." To investigate this mechanism, we have analyzed the sequences of the protein products of manually curated overlapping genes from 43 genera of unspliced RNA viruses infecting eukaryotes. Overlapping proteins have a sequence composition globally biased toward disorder-promoting amino acids and are predicted to contain significantly more structural disorder than nonoverlapping proteins. By analyzing the phylogenetic distribution of overlapping proteins, we were able to confirm that 17 of these had been created de novo and to study them individually. Most proteins created de novo are orphans (i.e., restricted to one species or genus). Almost all are accessory proteins that play a role in viral pathogenicity or spread, rather than proteins central to viral replication or structure. Most proteins created de novo are predicted to be fully disordered and have a highly unusual sequence composition. This suggests that some viral overlapping reading frames encoding hypothetical proteins with highly biased composition, often discarded as noncoding, might in fact encode proteins. Some proteins created de novo are predicted to be ordered, however, and whenever a three-dimensional structure of such a protein has been solved, it corresponds to a fold previously unobserved, suggesting that the study of these proteins could enhance our knowledge of protein space.
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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.