1,721,076 research outputs found
Asymmetric evolution in viral overlapping genes is a source of selective protein adaptation
No full textOverlapping 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
Prediction of two novel overlapping ORFs in the genome of SARS-CoV-2
No full textSix 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
New insights into the evolutionary features of viral overlapping genes by discriminant analysis
No full textOverlapping 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
Computational methods for inferring location and genealogy of overlapping genes in virus genomes: approaches and applications
Full text linkViruses 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
Origin, evolution and stability of overlapping genes in viruses: A systematic review
Full text linkDuring 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
Covariation of Amino Acid Substitutions in the HIV-1 Envelope Glycoprotein gp120 and the Antisense Protein ASP Associated with Coreceptor Usage
No full text: The tropism of the Human Immunodeficiency Virus type 1 (HIV-1) is determined by the use of either or both chemokine coreceptors CCR5 (R5) and CXCR4 (X4) for entry into the target cell. The ability of HIV-1 to bind R5 or X4 is determined primarily by the third variable loop (V3) of the viral envelope glycoprotein gp120. HIV-1 strains of pandemic group M contain an antisense gene termed asp, which overlaps env outside the region encoding the V3 loop. We previously showed that the ASP protein localizes on the envelope of infectious HIV-1 virions, suggesting that it may play a role in viral entry. In this study, we first developed a statistical method to predict coreceptor tropism based on Fisher's linear discriminant analysis. We obtained three linear discriminant functions able to predict coreceptor tropism with high accuracy (94.4%) when applied to a training dataset of V3 sequences of known tropism. Using these functions, we predicted the tropism in a dataset of HIV-1 strains containing a full-length asp gene. In the amino acid sequence of ASP proteins expressed from these asp genes, we identified five positions with substitutions significantly associated with viral tropism. Interestingly, we found that these substitutions correlate significantly with substitutions at six amino acid positions of the V3 loop domain associated with tropism. Altogether, our computational analyses identify ASP amino acid signatures coevolving with V3 and potentially affecting HIV-1 tropism, which can be validated through in vitro and in vivo experiments
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
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