Evidence map›Paper›PMID 30339683›Full record

ArticlePloS one2018

Overlapping genes and the proteins they encode differ significantly in their sequence composition from non-overlapping genes.

Angelo Pavesi, Alberto Vianelli, Nicola Chirico, Yiming Bao, Olga Blinkova, Robert Belshaw, Andrew Firth, David Karlin

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
31citing papers in PubMed, 1 pooled it
12.2field-weighted citation impact, top 2% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

31 citing papers in PubMed, 1 synthesis or guideline pooled it, 66 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Article
  4. Article
  5. Orphan genes are not a distinct biological entity.BioEssays : news and reviews in molecular, cellular and developmental biology · 2025
    Review
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  20. Understanding small ORF diversity through a comprehensive transcription feature classification.DNA research : an international journal for rapid publication of reports on genes and genomes · 2021
    Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors at 6 institutions in 4 countries.

Angelo PavesiDepartment of Chemistry, Life Sciences and Environmental Sustainability, University of Parma, Parma, Italy.
Alberto VianelliDepartment of Theoretical and Applied Sciences, University of Insubria, Varese, Italy.ORCID 0000-0002-5206-3164
Nicola ChiricoDepartment of Theoretical and Applied Sciences, University of Insubria, Varese, Italy.
Yiming BaoBIG Data Center, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, China.
Olga BlinkovaNational Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD, United States of America.
Robert BelshawSchool of Biomedical & Healthcare Sciences, Plymouth University Peninsula Schools of Medicine and Dentistry (PUPSMD), Plymouth, United Kingdom.
Andrew FirthDepartment of Pathology, Division of Virology, University of Cambridge, Cambridge, United Kingdom.
David KarlinDepartment of Zoology, University of Oxford, Oxford, United Kingdom.
University of Insubria · ITBeijing Institute of Genomics · CNNational Institutes of Health · USUniversity of Cambridge · GBUniversity of Oxford · GBUniversity of Parma · IT

Funding

National Biomedical Information ServicesZIHLM200888 · NLM · NATIONAL LIBRARY OF MEDICINE · PI PALTOO, DINA · 2009 to 2025
$5200.7M
Wellcome TrustWellcome Trust 090005Wellcome Trust 106207
6 · The paper itself

Abstract

Overlapping genes represent a fascinating evolutionary puzzle, since they encode two functionally unrelated proteins from the same DNA sequence. They originate by a mechanism of overprinting, in which point mutations in an existing frame allow the expression (the "birth") of a completely new protein from a second frame. In viruses, in which overlapping genes are abundant, these new proteins often play a critical role in infection, yet they are frequently overlooked during genome annotation. This results in erroneous interpretation of mutational studies and in a significant waste of resources. Therefore, overlapping genes need to be correctly detected, especially since they are now thought to be abundant also in eukaryotes. Developing better detection methods and conducting systematic evolutionary studies require a large, reliable benchmark dataset of known cases. We thus assembled a high-quality dataset of 80 viral overlapping genes whose expression is experimentally proven. Many of them were not present in databases. We found that overall, overlapping genes differ significantly from non-overlapping genes in their nucleotide and amino acid composition. In particular, the proteins they encode are enriched in high-degeneracy amino acids and depleted in low-degeneracy ones, which may alleviate the evolutionary constraints acting on overlapping genes. Principal component analysis revealed that the vast majority of overlapping genes follow a similar composition bias, despite their heterogeneity in length and function. Six proven mammalian overlapping genes also followed this bias. We propose that this apparently near-universal composition bias may either favour the birth of overlapping genes, or/and result from selection pressure acting on them.

Indexed as

Evolution, MolecularAmino Acid SequenceAnimalsGenes, OverlappingGenes, ViralMammalsMutationOpen Reading FramesPrincipal Component AnalysisProteinsProteins

Identifiers

PMID30339683
PMCPMC6195259
OpenAlexW2897300788

What OpenQuestion holds

Textmetadata
LicenceCC0
Read underepoch 390

Registered trials

None linked

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.