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  1. Article ; Online: Creation of the HIV-1 antisense gene

    Pavesi, Angelo / Romerio, Fabio

    Microbiology spectrum

    2024  Volume 12, Issue 2, Page(s) e0380223

    Abstract: Despite being first identified more than three decades ago, the antisense ... ...

    Abstract Despite being first identified more than three decades ago, the antisense gene
    MeSH term(s) Animals ; HIV-1/genetics ; Pandemics ; Codon ; Open Reading Frames ; Disease Progression
    Chemical Substances Codon
    Language English
    Publishing date 2024-01-17
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2807133-5
    ISSN 2165-0497 ; 2165-0497
    ISSN (online) 2165-0497
    ISSN 2165-0497
    DOI 10.1128/spectrum.03802-23
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Origin, Evolution and Stability of Overlapping Genes in Viruses: A Systematic Review.

    Pavesi, Angelo

    Genes

    2021  Volume 12, Issue 6

    Abstract: During their long evolutionary history viruses generated many ... ...

    Abstract During their long evolutionary history viruses generated many proteins
    MeSH term(s) Genes, Viral ; Mutation Rate ; Phylogeny ; Selection, Genetic ; Viruses/classification ; Viruses/genetics
    Language English
    Publishing date 2021-05-26
    Publishing country Switzerland
    Document type Journal Article ; Systematic Review
    ZDB-ID 2527218-4
    ISSN 2073-4425 ; 2073-4425
    ISSN (online) 2073-4425
    ISSN 2073-4425
    DOI 10.3390/genes12060809
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Computational methods for inferring location and genealogy of overlapping genes in virus genomes: approaches and applications.

    Pavesi, Angelo

    Current opinion in virology

    2021  Volume 52, Page(s) 1–8

    Abstract: Viruses may evolve to increase the amount of encoded genetic information by means of overlapping genes, which utilize several reading frames. Such overlapping genes may be especially impactful for genomes of small size, often serving a source of novel ... ...

    Abstract Viruses may evolve to increase the amount of encoded genetic information by means of overlapping genes, which utilize several reading frames. Such overlapping genes may be especially impactful for genomes of small size, often serving a source of novel accessory proteins, some of which play a crucial role in viral pathogenicity or in promoting the systemic spread of virus. Diverse genome-based metrics were proposed to facilitate recognition of overlapping genes that otherwise may be overlooked during genome annotation. They can detect the atypical codon bias associated with the overlap (e.g. a statistically significant reduction in variability at synonymous sites) or other sequence-composition features peculiar to overlapping genes. In this review, I compare nine computational methods, discuss their strengths and limitations, and survey how they were applied to detect candidate overlapping genes in the genome of SARS-CoV-2, the etiological agent of COVID-19 pandemic.
    MeSH term(s) COVID-19 ; Computational Biology ; Evolution, Molecular ; Genes, Overlapping ; Genome, Viral ; Humans ; Open Reading Frames ; Pandemics ; SARS-CoV-2
    Language English
    Publishing date 2021-11-16
    Publishing country Netherlands
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 2611378-8
    ISSN 1879-6265 ; 1879-6257
    ISSN (online) 1879-6265
    ISSN 1879-6257
    DOI 10.1016/j.coviro.2021.10.009
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Prediction of two novel overlapping ORFs in the genome of SARS-CoV-2.

    Pavesi, Angelo

    Virology

    2021  Volume 562, Page(s) 149–157

    Abstract: Six candidate overlapping genes have been detected in SARS-CoV-2, yet current methods struggle to detect overlapping genes that recently originated. However, such genes might encode proteins beneficial to the virus, and provide a model system to ... ...

    Abstract Six candidate overlapping genes have been detected in SARS-CoV-2, yet current methods struggle to detect overlapping genes that recently originated. However, such genes might encode proteins beneficial to the virus, and provide a model system to understand gene birth. To complement existing detection methods, I first demonstrated that selection pressure to avoid stop codons in alternative reading frames is a driving force in the origin and retention of overlapping genes. I then built a detection method, CodScr, based on this selection pressure. Finally, I combined CodScr with methods that detect other properties of overlapping genes, such as a biased nucleotide and amino acid composition. I detected two novel ORFs (ORF-Sh and ORF-Mh), overlapping the spike and membrane genes respectively, which are under selection pressure and may be beneficial to SARS-CoV-2. ORF-Sh and ORF-Mh are present, as ORF uninterrupted by stop codons, in 100% and 95% of the SARS-CoV-2 genomes, respectively.
    MeSH term(s) Codon Usage ; Evolution, Molecular ; Genes, Overlapping ; Genome, Viral ; Open Reading Frames ; SARS-CoV-2/genetics ; Spike Glycoprotein, Coronavirus/chemistry ; Spike Glycoprotein, Coronavirus/genetics ; Statistics as Topic
    Chemical Substances Spike Glycoprotein, Coronavirus
    Language English
    Publishing date 2021-07-28
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 200425-2
    ISSN 1096-0341 ; 0042-6822
    ISSN (online) 1096-0341
    ISSN 0042-6822
    DOI 10.1016/j.virol.2021.07.011
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Different Patterns of Codon Usage and Amino Acid Composition across Primate Lentiviruses.

    Pavesi, Angelo / Romerio, Fabio

    Viruses

    2023  Volume 15, Issue 7

    Abstract: A common feature of the ... ...

    Abstract A common feature of the mammalian
    MeSH term(s) Animals ; Amino Acids/genetics ; Lentiviruses, Primate/genetics ; Codon Usage ; Codon ; Lentivirus/genetics ; HIV-1/genetics ; Adenine ; Guanine ; Mammals
    Chemical Substances Amino Acids ; Codon ; Adenine (JAC85A2161) ; Guanine (5Z93L87A1R)
    Language English
    Publishing date 2023-07-20
    Publishing country Switzerland
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2516098-9
    ISSN 1999-4915 ; 1999-4915
    ISSN (online) 1999-4915
    ISSN 1999-4915
    DOI 10.3390/v15071580
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: New insights into the evolutionary features of viral overlapping genes by discriminant analysis.

    Pavesi, Angelo

    Virology

    2020  Volume 546, Page(s) 51–66

    Abstract: Overlapping genes originate by a mechanism of overprinting, in which nucleotide substitutions in a pre-existing frame induce the expression of a de novo protein from an alternative frame. In this study, I assembled a dataset of 319 viral overlapping ... ...

    Abstract Overlapping genes originate by a mechanism of overprinting, in which nucleotide substitutions in a pre-existing frame induce the expression of a de novo protein from an alternative frame. In this study, I assembled a dataset of 319 viral overlapping genes, which included 82 overlaps whose expression is experimentally known and the respective 237 homologs. Principal component analysis revealed that overlapping genes have a common pattern of nucleotide and amino acid composition. Discriminant analysis separated overlapping from non-overlapping genes with an accuracy of 97%. When applied to overlapping genes with known genealogy, it separated ancestral from de novo frames with an accuracy close to 100%. This high discriminant power was crucial to computationally design variants of de novo viral proteins known to possess selective anticancer toxicity (apoptin) or protection against neurodegeneration (X protein), as well as to detect two new potential overlapping genes in the genome of the new coronavirus SARS-CoV-2.
    MeSH term(s) Algorithms ; Amino Acid Sequence ; Base Sequence ; Betacoronavirus/genetics ; Computational Biology ; Computer Simulation ; Discriminant Analysis ; Evolution, Molecular ; Genes, Overlapping ; Genes, Viral ; Least-Squares Analysis ; Principal Component Analysis ; SARS-CoV-2
    Keywords covid19
    Language English
    Publishing date 2020-04-02
    Publishing country United States
    Document type Journal Article
    ZDB-ID 200425-2
    ISSN 1096-0341 ; 0042-6822
    ISSN (online) 1096-0341
    ISSN 0042-6822
    DOI 10.1016/j.virol.2020.03.007
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Asymmetric evolution in viral overlapping genes is a source of selective protein adaptation.

    Pavesi, Angelo

    Virology

    2019  Volume 532, Page(s) 39–47

    Abstract: Overlapping genes represent an intriguing puzzle, as they encode two proteins whose ability to evolve is constrained by each other. Overlapping genes can undergo "symmetric evolution" (similar selection pressures on the two proteins) or "asymmetric ... ...

    Abstract Overlapping genes represent an intriguing puzzle, as they encode two proteins whose ability to evolve is constrained by each other. Overlapping genes can undergo "symmetric evolution" (similar selection pressures on the two proteins) or "asymmetric evolution" (significantly different selection pressures on the two proteins). By sequence analysis of 75 pairs of homologous viral overlapping genes, I evaluated their accordance with one or the other model. Analysis of nucleotide and amino acid sequences revealed that half of overlaps undergo asymmetric evolution, as the protein from one frame shows a number of substitutions significantly higher than that of the protein from the other frame. Interestingly, the most variable protein (often known to interact with the host proteins) appeared to be encoded by the de novo frame in all cases examined. These findings suggest that overlapping genes, besides to increase the coding ability of viruses, are also a source of selective protein adaptation.
    MeSH term(s) Amino Acid Sequence ; Base Sequence ; Evolution, Molecular ; Genes, Overlapping ; Genes, Viral ; Genetic Variation ; Models, Genetic ; Open Reading Frames ; Phylogeny ; Selection, Genetic ; Viral Proteins/genetics ; Viruses/classification ; Viruses/genetics
    Chemical Substances Viral Proteins
    Keywords covid19
    Language English
    Publishing date 2019-04-03
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 200425-2
    ISSN 1096-0341 ; 0042-6822
    ISSN (online) 1096-0341
    ISSN 0042-6822
    DOI 10.1016/j.virol.2019.03.017
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article: Prediction of two novel overlapping ORFs in the genome of SARS-CoV-2

    Pavesi, Angelo

    Virology. 2021 Oct., v. 562

    2021  

    Abstract: Six candidate overlapping genes have been detected in SARS-CoV-2, yet current methods struggle to detect overlapping genes that recently originated. However, such genes might encode proteins beneficial to the virus, and provide a model system to ... ...

    Abstract Six candidate overlapping genes have been detected in SARS-CoV-2, yet current methods struggle to detect overlapping genes that recently originated. However, such genes might encode proteins beneficial to the virus, and provide a model system to understand gene birth. To complement existing detection methods, I first demonstrated that selection pressure to avoid stop codons in alternative reading frames is a driving force in the origin and retention of overlapping genes. I then built a detection method, CodScr, based on this selection pressure. Finally, I combined CodScr with methods that detect other properties of overlapping genes, such as a biased nucleotide and amino acid composition. I detected two novel ORFs (ORF-Sh and ORF-Mh), overlapping the spike and membrane genes respectively, which are under selection pressure and may be beneficial to SARS-CoV-2. ORF-Sh and ORF-Mh are present, as ORF uninterrupted by stop codons, in 100% and 95% of the SARS-CoV-2 genomes, respectively.
    Keywords Severe acute respiratory syndrome coronavirus 2 ; amino acid composition ; prediction ; selection pressure ; stop codon ; virology ; viruses
    Language English
    Dates of publication 2021-10
    Size p. 149-157.
    Publishing place Elsevier Inc.
    Document type Article
    ZDB-ID 200425-2
    ISSN 1096-0341 ; 0042-6822
    ISSN (online) 1096-0341
    ISSN 0042-6822
    DOI 10.1016/j.virol.2021.07.011
    Database NAL-Catalogue (AGRICOLA)

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  9. Article: Origin, Evolution and Stability of Overlapping Genes in Viruses: A Systematic Review

    Pavesi, Angelo

    Genes. 2021 May 26, v. 12, no. 6

    2021  

    Abstract: During their long evolutionary history viruses generated many proteins de novo by a mechanism called “overprinting”. Overprinting is a process in which critical nucleotide substitutions in a pre-existing gene can induce the expression of a novel protein ... ...

    Abstract During their long evolutionary history viruses generated many proteins de novo by a mechanism called “overprinting”. Overprinting is a process in which critical nucleotide substitutions in a pre-existing gene can induce the expression of a novel protein by translation of an alternative open reading frame (ORF). Overlapping genes represent an intriguing example of adaptive conflict, because they simultaneously encode two proteins whose freedom to change is constrained by each other. However, overlapping genes are also a source of genetic novelties, as the constraints under which alternative ORFs evolve can give rise to proteins with unusual sequence properties, most importantly the potential for novel functions. Starting with the discovery of overlapping genes in phages infecting Escherichia coli, this review covers a range of studies dealing with detection of overlapping genes in small eukaryotic viruses (genomic length below 30 kb) and recognition of their critical role in the evolution of pathogenicity. Origin of overlapping genes, what factors favor their birth and retention, and how they manage their inherent adaptive conflict are extensively reviewed. Special attention is paid to the assembly of overlapping genes into ad hoc databases, suitable for future studies, and to the development of statistical methods for exploring viral genome sequences in search of undiscovered overlaps.
    Keywords Escherichia coli ; evolution ; genes ; genomics ; pathogenicity ; systematic review ; viral genome
    Language English
    Dates of publication 2021-0526
    Publishing place Multidisciplinary Digital Publishing Institute
    Document type Article
    ZDB-ID 2527218-4
    ISSN 2073-4425
    ISSN 2073-4425
    DOI 10.3390/genes12060809
    Database NAL-Catalogue (AGRICOLA)

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  10. Article ; Online: Extending the Coding Potential of Viral Genomes with Overlapping Antisense ORFs: A Case for the De Novo Creation of the Gene Encoding the Antisense Protein ASP of HIV-1.

    Pavesi, Angelo / Romerio, Fabio

    Viruses

    2022  Volume 14, Issue 1

    Abstract: Gene overprinting occurs when point mutations within a genomic region with an existing coding sequence create a new one in another reading frame. This process is quite frequent in viral genomes either to maximize the amount of information that they ... ...

    Abstract Gene overprinting occurs when point mutations within a genomic region with an existing coding sequence create a new one in another reading frame. This process is quite frequent in viral genomes either to maximize the amount of information that they encode or in response to strong selective pressure. The most frequent scenario involves two different reading frames in the same DNA strand (sense overlap). Much less frequent are cases of overlapping genes that are encoded on opposite DNA strands (antisense overlap). One such example is the antisense ORF, asp in the minus strand of the HIV-1 genome overlapping the env gene. The asp gene is highly conserved in pandemic HIV-1 strains of group M, and it is absent in non-pandemic HIV-1 groups, HIV-2, and lentiviruses infecting non-human primates, suggesting that the ~190-amino acid protein that is expressed from this gene (ASP) may play a role in virus spread. While the function of ASP in the virus life cycle remains to be elucidated, mounting evidence from several research groups indicates that ASP is expressed in vivo. There are two alternative hypotheses that could be envisioned to explain the origin of the asp ORF. On one hand, asp may have originally been present in the ancestor of contemporary lentiviruses, and subsequently lost in all descendants except for most HIV-1 strains of group M due to selective advantage. Alternatively, the asp ORF may have originated very recently with the emergence of group M HIV-1 strains from SIVcpz. Here, we used a combination of computational and statistical approaches to study the genomic region of env in primate lentiviruses to shed light on the origin, structure, and sequence evolution of the asp ORF. The results emerging from our studies support the hypothesis of a recent de novo addition of the antisense ORF to the HIV-1 genome through a process that entailed progressive removal of existing internal stop codons from SIV strains to HIV-1 strains of group M, and fine tuning of the codon sequence in env that reduced the chances of new stop codons occurring in asp. Altogether, the study supports the notion that the HIV-1 asp gene encodes an accessory protein, providing a selective advantage to the virus.
    MeSH term(s) Base Sequence ; Codon ; Evolution, Molecular ; Genome, Viral ; HIV Seropositivity/genetics ; HIV-1/genetics ; Human Immunodeficiency Virus Proteins/genetics ; Humans ; Open Reading Frames ; Viral Envelope Proteins/genetics
    Chemical Substances ASP protein, HIV-1 ; Codon ; Human Immunodeficiency Virus Proteins ; Viral Envelope Proteins
    Language English
    Publishing date 2022-01-14
    Publishing country Switzerland
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2516098-9
    ISSN 1999-4915 ; 1999-4915
    ISSN (online) 1999-4915
    ISSN 1999-4915
    DOI 10.3390/v14010146
    Database MEDical Literature Analysis and Retrieval System OnLINE

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