Search results for "MUTATION"
showing 10 items of 2830 documents
Unequal distribution of RT-PCR artifacts along the E1-E2 region of Hepatitis C virus.
2009
Although viral variability studies have focused traditionally on consensus sequences, the relevance of molecular clone sequences for studying viral evolution at the intra-host level is being increasingly recognized. However, for this approach to be reliable, RT-PCR artifacts do not have to contribute excessively to the observed variability. Molecular clone sequences were obtained from an in vitro transcript to estimate the maximum error rate associated to RT-PCR for the Hepatitis C virus (HCV) E1-E2 region. On average, the frequency of RT-PCR errors was one order of magnitude lower than the level of intra-host genetic variability observed in samples from an HCV outbreak. However, RT-PCR err…
An unusually high substitution rate in transplant-associated BK polyomavirus in vivo is further concentrated in HLA-C-bound viral peptides
2018
Infection with human BK polyomavirus, a small double-stranded DNA virus, potentially results in severe complications in immunocompromised patients. Here, we describe the in vivo variability and evolution of the BK polyomavirus by deep sequencing. Our data reveal the highest genomic evolutionary rate described in double-stranded DNA viruses, i.e., 10−3–10−5 substitutions per nucleotide site per year. High mutation rates in viruses allow their escape from immune surveillance and adaptation to new hosts. By combining mutational landscapes across viral genomes with in silico prediction of viral peptides, we demonstrate the presence of significantly more coding substitutions within predicted cog…
The contribution of epistasis to the architecture of fitness in an RNA virus
2004
4 pages, 2 figures.-- PMID: 15492220 [PubMed].-- PMCID: PMC524436.-- Additional information (Suppl. table S1: Relevant information about each single- and double-nucleotide substitution mutant created) available at: http://www.pnas.org/content/101/43/15376/suppl/DC1
Large-scale analysis of SARS-CoV-2 spike-glycoprotein mutants demonstrates the need for continuous screening of virus isolates
2021
Due to the widespread of the COVID-19 pandemic, the SARS-CoV-2 genome is evolving in diverse human populations. Several studies already reported different strains and an increase in the mutation rate. Particularly, mutations in SARS-CoV-2 spike-glycoprotein are of great interest as it mediates infection in human and recently approved mRNA vaccines are designed to induce immune responses against it. We analyzed 1,036,030 SARS-CoV-2 genome assemblies and 30,806 NGS datasets from GISAID and European Nucleotide Archive (ENA) focusing on non-synonymous mutations in the spike protein. Only around 2.5% of the samples contained the wild-type spike protein with no variation from the reference. Among…
Variability and host-dependency of RNA virus mutation rates
2015
Los virus de ARN pueden infectar todo tipo de organismos, desde los procariotas a los eucariotas superiores, y estos agentes infecciosos parecen particularmente propensos a causar enfermedades emergentes tanto en humanos, animales, como en plantas. Su habilidad para escapar del sistema inmunitario, evadir estrategias antivirales o infectar a nuevas especies son aspecto más de su rápida evolución. Por lo tanto, comprender los procesos básicos del la evolución de los virus de ARN podría ayudar en el diseño de nuevas estrategias antivirales. Una de las principales características de los virus de ARN es su tasa de mutación extremadamente alta. De hecho, la alta diversidad genética de las poblac…
Catalytic Reaction Mechanism in Native and Mutant Catechol- O-methyltransferase from the Adaptive String Method and Mean Reaction Force Analysis.
2018
Catechol- O-methyltransferase is an enzyme that catalyzes the methylation reaction of dopamine by S-adenosylmethionine, increasing the reaction rate by almost 16 orders of magnitude compared to the reaction in aqueous solution. Here, we combine the recently introduced adaptive string method and the mean reaction force method, in combination with the structural and electronic descriptors to characterize the reaction mechanism. The catalytic effect of the enzyme is addressed by the comparison of the reaction in the human wild-type enzyme, in the less effective Y68A mutant, and in aqueous solution. The influence of these different environments at different stages of the chemical process and th…
A statistical analysis of the three-fold evolution of genomic compression through frame overlaps in prokaryotes
2007
Abstract Background Among microbial genomes, genetic information is frequently compressed, exploiting redundancies in the genetic code in order to store information in overlapping genes. We investigate the length, phase and orientation properties of overlap in 58 prokaryotic species evaluating neutral and selective mechanisms of evolution. Results Using a variety of statistical null models we find patterns of compressive coding that can not be explained purely in terms of the selective processes favoring genome minimization or translational coupling. The distribution of overlap lengths follows a fat-tailed distribution, in which a significant proportion of overlaps are in excess of 100 base…
A New Type of Cytokine Receptor Antagonist Directly Targeting gp130
1998
The interleukin-6-type family of cytokines bind to receptor complexes that share gp130 as a common signal-transducing subunit. So far, receptor antagonists for interleukin-6-type cytokines have been constructed that still bind to the specific ligand binding subunit of the receptor complex, but have lost the ability to stimulate gp130. Such receptor antagonists compete for a specific receptor of a member of the cytokine family. Interleukin-6 only binds to gp130 when complexed with the interleukin-6 receptor that exists as a membrane bound and soluble molecule. Here we have constructed fusion proteins that consist of the soluble form of the human interleukin-6 receptor covalently linked to in…
Characterization of a Naturally Occurring Breast Cancer Subset Enriched in Epithelial-to-Mesenchymal Transition and Stem Cell Characteristics
2009
Abstract Metaplastic breast cancers (MBC) are aggressive, chemoresistant tumors characterized by lineage plasticity. To advance understanding of their pathogenesis and relatedness to other breast cancer subtypes, 28 MBCs were compared with common breast cancers using comparative genomic hybridization, transcriptional profiling, and reverse-phase protein arrays and by sequencing for common breast cancer mutations. MBCs showed unique DNA copy number aberrations compared with common breast cancers. PIK3CA mutations were detected in 9 of 19 MBCs (47.4%) versus 80 of 232 hormone receptor–positive cancers (34.5%; P = 0.32), 17 of 75 HER-2–positive samples (22.7%; P = 0.04), 20 of 240 basal-like c…
Misfolded vasopressin V2 receptors caused by extracellular point mutations entail congenital nephrogenic diabetes insipidus.
2000
Vasopressin V2 receptor mutants from three different patients with congenital nephrogenic diabetes insipidus phenotypes were investigated after expression in COS cells. The amino acid exchanges within the human V2 receptor are located in the second extracellular loop (T204N, Y205C and V206D). Confocal microscopy showed that all receptor mutants were strongly expressed but mainly located within the cell. Residual binding capacity for the antidiuretic hormone arginine vasopressin (AVP) could only be detected for the T204N mutant and was 10-fold lower than for the wild-type receptor. Stimulation of transfected cells with 1 microM AVP showed that the T204N mutant was able to activate the adenyl…