ArticleProceedings of the National Academy of Sciences of the United States of America2013
Identification of an overprinting gene in Merkel cell polyomavirus provides evolutionary insight into the birth of viral genes.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 99 papers.
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99 citing papers in PubMed, 174 citations in OpenAlex.
- Viruses and the host replisome: discovering oncogenic mechanisms of small DNA tumor viruses.Journal of virology · 2026Review
- A short intrinsically disordered domain of MCPyV ALTO regulates TBK1 signaling during MCPyV infection.Journal of virology · 2025Article
- E2F1-3 activate Merkel cell polyomavirus early transcription and replication.bioRxiv : the preprint server for biology · 2025Article
- De Novo Gene Emergence: Summary, Classification, and Challenges of Current Methods.Genome biology and evolution · 2025Review
- Genome integration of human DNA oncoviruses.Journal of virology · 2025Review
- Recent advances in discovery and functional analysis of the small proteins and microRNA expressed by polyomaviruses.Virology · 2025Review
- Complete Genomes of DNA Viruses in Fecal Samples from Small Terrestrial Mammals in Spain.Viruses · 2024Article
- Polyomavirus ALTOs, but not MTs, downregulate viral early gene expression by activating the NF-κB pathway.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Merkel cell polyomavirus small tumor antigen contributes to immune evasion by interfering with type I interferon signaling.PLoS pathogens · 2024Article
- Merkel cell polyomavirus protein ALTO modulates TBK1 activity to support persistent infection.PLoS pathogens · 2024Article
- The small tumor antigen of Merkel cell polyomavirus accomplishes cellular transformation by uniquely localizing to the nucleus despite the absence of a known nuclear localization signal.Virology journal · 2024Article
- Iron‑sulfur clusters in viral proteins: Exploring their elusive nature, roles and new avenues for targeting infections.Biochimica et biophysica acta. Molecular cell research · 2024Review
- Polyomavirus ALTOs, but not MTs, downregulate viral early gene expression by activating the NF-κB pathway.bioRxiv : the preprint server for biology · 2024Article
- Widespread Horizontal Gene Transfer Among Animal Viruses.bioRxiv : the preprint server for biology · 2024Article
- Merkel cell carcinoma: updates in tumor biology, emerging therapies, and preclinical models.Frontiers in oncology · 2024Review
- Membrane-bound Merkel cell polyomavirus middle T protein constitutively activates PLCγ1 signaling through Src-family kinases.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Phosphorylation of Human Polyomavirus Large and Small T Antigens: An Ignored Research Field.Viruses · 2023Review
- Critical involvement of circular RNAs in virus-associated cancers.Genes & diseases · 2023Review
- Identification and characterization of a polyomavirus in the thornback skate (Raja clavata).Virology journal · 2023Article
- Characterization of molecular mechanisms driving Merkel cell polyomavirus oncogene transcription and tumorigenic potential.PLoS pathogens · 2023Article
39 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 2 institutions in 3 countries.
Funding
Abstract
Many viruses use overprinting (alternate reading frame utilization) as a means to increase protein diversity in genomes severely constrained by size. However, the evolutionary steps that facilitate the de novo generation of a novel protein within an ancestral ORF have remained poorly characterized. Here, we describe the identification of an overprinting gene, expressed from an Alternate frame of the Large T Open reading frame (ALTO) in the early region of Merkel cell polyomavirus (MCPyV), the causative agent of most Merkel cell carcinomas. ALTO is expressed during, but not required for, replication of the MCPyV genome. Phylogenetic analysis reveals that ALTO is evolutionarily related to the middle T antigen of murine polyomavirus despite almost no sequence similarity. ALTO/MT arose de novo by overprinting of the second exon of T antigen in the common ancestor of a large clade of mammalian polyomaviruses. Taking advantage of the low evolutionary divergence and diverse sampling of polyomaviruses, we propose evolutionary transitions that likely gave birth to this protein. We suggest that two highly constrained regions of the large T antigen ORF provided a start codon and C-terminal hydrophobic motif necessary for cellular localization of ALTO. These two key features, together with stochastic erasure of intervening stop codons, resulted in a unique protein-coding capacity that has been preserved ever since its birth. Our study not only reveals a previously undefined protein encoded by several polyomaviruses including MCPyV, but also provides insight into de novo protein evolution.
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