ArticleGenome biology2015
FRESCo: finding regions of excess synonymous constraint in diverse viruses.
Article in Genome biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers, 1 of them a synthesis that pooled it.
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Who cites it
30 citing papers in PubMed, 1 synthesis or guideline pooled it, 43 citations in OpenAlex.
- Pooled it
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- Parvovirus B19 and Human Parvovirus 4 Encode Similar Proteins in a Reading Frame Overlapping the VP1 Capsid Gene.Viruses · 2024Article
- Alternative Reading Frames are an Underappreciated Source of Protein Sequence Novelty.Journal of molecular evolution · 2023Review
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- Identification of Orbivirus Non-Structural Protein 5 (NS5), Its Role and Interaction with RNA/DNA in Infected Cells.International journal of molecular sciences · 2023Article
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- Computational methods for inferring location and genealogy of overlapping genes in virus genomes: approaches and applications.Current opinion in virology · 2022Review
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- Genetic and phylogenetic characterization of polycistronic dsRNA segment-10 of bluetongue virus isolates from India between 1985 and 2011.Virus genes · 2021Article
- SARS-CoV-2 gene content and COVID-19 mutation impact by comparing 44 Sarbecovirus genomes.Nature communications · 2021Article
- Genomic RNA Elements Drive Phase Separation of the SARS-CoV-2 Nucleocapsid.Molecular cell · 2020Article
- Evidence for secondary-variant genetic burden and non-random distribution across biological modules in a recessive ciliopathy.Nature genetics · 2020Article
- SARS-CoV-2 gene content and COVID-19 mutation impact by comparing 44 Sarbecovirus genomes.Research square · 2020Article
- SARS-CoV-2 gene content and COVID-19 mutation impact by comparing 44 Sarbecovirus genomes.bioRxiv : the preprint server for biology · 2020Article
- OLGenie: Estimating Natural Selection to Predict Functional Overlapping Genes.Molecular biology and evolution · 2020Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundThe increasing availability of sequence data for many viruses provides power to detect regions under unusual evolutionary constraint at a high resolution. One approach leverages the synonymous substitution rate as a signature to pinpoint genic regions encoding overlapping or embedded functional elements. Protein-coding regions in viral genomes often contain overlapping RNA structural elements, reading frames, regulatory elements, microRNAs, and packaging signals. Synonymous substitutions in these regions would be selectively disfavored and thus these regions are characterized by excess synonymous constraint. Codon choice can also modulate transcriptional efficiency, translational accuracy, and protein folding.
resultsWe developed a phylogenetic codon model-based framework, FRESCo, designed to find regions of excess synonymous constraint in short, deep alignments, such as individual viral genes across many sequenced isolates. We demonstrated the high specificity of our approach on simulated data and applied our framework to the protein-coding regions of approximately 30 distinct species of viruses with diverse genome architectures.
conclusionsFRESCo recovers known multifunctional regions in well-characterized viruses such as hepatitis B virus, poliovirus, and West Nile virus, often at a single-codon resolution, and predicts many novel functional elements overlapping viral genes, including in Lassa and Ebola viruses. In a number of viruses, the synonymously constrained regions that we identified also display conserved, stable predicted RNA structures, including putative novel elements in multiple viral species.
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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.