ArticleProceedings of the National Academy of Sciences of the United States of America2007
Rapid asymmetric evolution of a dual-coding tumor suppressor INK4a/ARF locus contradicts its function.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers, 1 of them a synthesis that pooled it.
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Who cites it
16 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Pooled it
- Pervasive non-triplet alternative splicing drives functional isoform diversity.Nature communications · 2026Article
- Alternatively Spliced Dual-Coding Regions Contribute to the Human Gene Regulatory Program.bioRxiv : the preprint server for biology · 2026Article
- From data to publication in a browser with BRC-Analytics: Evolutionary dynamics of coding overlaps in measles virus.bioRxiv : the preprint server for biology · 2025Article
- Comprehensive expression analysis for the core cell cycle regulators in the chicken embryo reveals novel tissue-specific synexpression groups and similarities and differences with expression in mouse, frog and zebrafish.Journal of anatomy · 2022Article
- Stepwise Evolution and Exceptional Conservation of ORF1a/b Overlap in Coronaviruses.Molecular biology and evolution · 2021Article
- Stepwise evolution and exceptional conservation of ORF1a/b overlap in coronaviruses.bioRxiv : the preprint server for biology · 2021Article
- Asymmetric evolution in viral overlapping genes is a source of selective protein adaptation.Virology · 2019Article
- Genotype-Specific Evolution of Hepatitis E Virus.Journal of virology · 2017Article
- Overlapping genes: a new strategy of thermophilic stress tolerance in prokaryotes.Extremophiles : life under extreme conditions · 2015Article
- INK4 locus of the tumor-resistant rodent, the naked mole rat, expresses a functional p15/p16 hybrid isoform.Proceedings of the National Academy of Sciences of the United States of America · 2015Article
- FMN2 is a novel regulator of the cyclin-dependent kinase inhibitor p21.Cell cycle (Georgetown, Tex.) · 2013Article
- Is there a twelfth protein-coding gene in the genome of influenza A? A selection-based approach to the detection of overlapping genes in closely related sequences.Journal of molecular evolution · 2011Article
- Detection of functional overlapping genes: simulation and case studies.Journal of molecular evolution · 2010Article
- Dual coding in alternative reading frames correlates with intrinsic protein disorder.Proceedings of the National Academy of Sciences of the United States of America · 2010Article
- High-resolution mapping of evolutionary trajectories in a phage.Genome biology and evolution · 2009Article
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4 authors.
Funding
Abstract
INK4a/ARF tumor suppressor locus encodes two protein products, INK4a and ARF, essential for controlling tumorigenesis and mutated in more than half of human cancers. There is no resemblance between the two proteins: their coding regions are assembled by alternative splicing of two mutually exclusive 5' exons into a constitutive one containing overlapping out-of-phase reading frames. We show that the dual-coding arrangement conflicts with the high cost of mutations within INK4a/ARF. Unexpectedly, the locus evolves rapidly and asymmetrically, with ARF accumulating the majority of amino acid replacements. Rapid evolution drives both INK4a and ARF proteins out of sync with other members of the RB and p53 tumor suppressor pathways, both of which are controlled by the locus. Yet, the asymmetric behavior may be an intrinsic property of dual-coding exons: INK4a/ARF closely mimics the evolution of 90 newly identified genes with similar dual-coding structure. Thus, the strong link between mutations in INK4a/ARF and cancer may be a direct consequence of the architecture of the locus.
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