Evolution of Codon Usage Bias in Henipaviruses Is Governed by Natural Selection and Is Host-Specific.
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ABSTRACT:
SUBMITTER: Kumar N
PROVIDER: S-EPMC6266499 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:The molecular evolutionary dynamics that shape hantaviruses' evolution are poorly understood even now, besides the contribution of virus-host interaction to their evolution remains an open question. Our study aimed to investigate these two aspects in Hantaan virus (HTNV)-the prototype of hantaviruses and an emerging zoonotic pathogen that infects humans, causing hemorrhagic fever with renal syndrome (HFRS): endemic in Far East Russia, China, and South Korea-via a comprehensive, phylogenetic-dependent codon usage analysis. We found that host- and natural reservoir-induced natural selection is the primary determinant of its biased codon choices, exceeding the mutational bias effect. The phylogenetic analysis of HTNV strains resulted in three distinct clades: South Korean, Russian, and Chinese. An effective number of codon (ENC) analysis showed a slightly biased codon usage in HTNV genomes. Nucleotide composition and RSCU analyses revealed a significant bias toward A/U nucleotides and A/U-ended codons, indicating the potential influence of mutational bias on the codon usage patterns of HTNV. Via ENC-plot, Parity Rule 2 (PR2), and neutrality plot analyses, we would conclude the presence of both mutation pressure and natural selection effect in shaping the codon usage patterns of HTNV; however, natural selection is the dominant factor influencing its codon usage bias. Codon adaptation index (CAI), Relative codon deoptimization index (RCDI), and Similarity Index (SiD) analyses uncovered the intense selection pressure from the host (Human) and natural reservoirs (Striped field mouse and Chinese white-bellied rat) in shaping HTNV biased codon choices. Our study clearly revealed the evolutionary processes in HTNV and the role of virus-host interaction in its evolution. Moreover, it opens the door for a more comprehensive codon usage analysis for all hantaviruses species to determine their molecular evolutionary dynamics and adaptability to several hosts and environments. We believe that our research will help in a better and deep understanding of HTNV evolution that will serve its future basic research and aid live attenuated vaccines design.
| S-EPMC8283416 | biostudies-literature
Project description:Codon usage bias (CUB)-preferential use of one of the synonymous codons, has been described in a wide range of organisms from bacteria to mammals, but it has not yet been studied in marine phytoplankton. CUB is thought to be caused by weak selection for translational accuracy and efficiency. Weak selection can overpower genetic drift only in species with large effective population sizes, such as Drosophila that has relatively strong CUB, while organisms with smaller population sizes (e.g., mammals) have weak CUB. Marine plankton species tend to have extremely large populations, suggesting that CUB should be very strong. Here we test this prediction and describe the patterns of codon usage in a wide range of diatom species belonging to 35 genera from 4 classes. We report that most of the diatom species studied have surprisingly modest CUB (mean Effective Number of Codons, ENC = 56), with some exceptions showing stronger codon bias (ENC = 44). Modest codon bias in most studied diatom species may reflect extreme disparity between astronomically large census and modest effective population size (Ne), with fluctuations in population size and linked selection limiting long-term Ne and rendering selection for optimal codons less efficient. For example, genetic diversity (pi ~0.02 at silent sites) in Skeletonema marinoi corresponds to Ne of about 10 million individuals, which is likely many orders of magnitude lower than its census size. Still, Ne ~107 should be large enough to make selection for optimal codons efficient. Thus, we propose that an alternative process-frequent changes of preferred codons, may be a more plausible reason for low CUB despite highly efficient selection for preferred codons in diatom populations. The shifts in the set of optimal codons should result in the changes of the direction of selection for codon usage, so the actual codon usage never catches up with the moving target of the optimal set of codons and the species never develop strong CUB. Indeed, we detected strong shifts in preferential codon usage within some diatom genera, with switches between preferentially GC-rich and AT-rich 3rd codon positions (GC3). For example, GC3 ranges from 0.6 to 1 in most Chaetoceros species, while for Chaetoceros dichaeta GC3 = 0.1. Both variation in selection intensity and mutation spectrum may drive such shifts in codon usage and limit the observed CUB. Our study represents the first genome-wide analysis of CUB in diatoms and the first such analysis for a major phytoplankton group.
| S-EPMC6896221 | biostudies-literature
Project description:Eighteen of the 20 amino acids are each encoded by more than one synonymous codon. Due to differential transfer RNA supply within the cell, synonymous codons are not used with equal frequency, a phenomenon termed codon usage bias (CUB). Previous studies have demonstrated that CUB of endogenous genes trans-regulates the translational efficiency of other genes. We hypothesized similar effects for CUB of exogenous genes on host translation, and tested it in the case of viral infection, a common form of naturally occurring exogenous gene translation. We analysed public Ribo-Seq datasets from virus-infected yeast and human cells and showed that virus CUB trans-regulated tRNA availability, and therefore the relative decoding time of codons. Manipulative experiments in yeast using 37 synonymous fluorescent proteins confirmed that an exogenous gene with CUB more similar to that of the host would apply decreased translational load on the host per unit of expression, whereas expression of the exogenous gene was elevated. The combination of these two effects was that exogenous genes with CUB overly similar to that of the host severely impeded host translation. Finally, using a manually curated list of viruses and natural and symptomatic hosts, we found that virus CUB tended to be more similar to that of symptomatic hosts than that of natural hosts, supporting a general deleterious effect of excessive CUB similarity between virus and host. Our work revealed repulsion between virus and host CUBs when they are overly similar, a previously unrecognized complexity in the coevolution of virus and host.
| S-EPMC7249751 | biostudies-literature
Project description:Severe acute respiratory syndrome has spread quickly throughout the world and was declared a pandemic by the World Health Organization (WHO). The pathogenic agent is a new coronavirus (SARS-CoV-2) that infects pulmonary cells with great effectiveness. In this study we focus on the codon composition for the viral protein synthesis and its relationship with the protein synthesis of the host. Our analysis reveals that SARS-CoV-2 preferred codons have poor representation of G or C nucleotides in the third position, a characteristic which could result in an unbalance in the tRNAs pools of the infected cells with serious implications in host protein synthesis. By integrating this observation with proteomic data from infected cells, we observe a reduced translation rate of host proteins associated with highly expressed genes and that they share the codon usage bias of the virus. The functional analysis of these genes suggests that this mechanism of epistasis can contribute to understanding how this virus evades the immune response and the etiology of some deleterious collateral effect as a result of the viral replication. In this manner, our finding contributes to the understanding of the SARS-CoV-2 pathogeny and could be useful for the design of a vaccine based on the live attenuated strategy.
| S-EPMC7468442 | biostudies-literature
Project description:Population genetic theory predicts that the efficacy of natural selection in a self-fertilizing species should be lower than its outcrossing relatives because of the reduction in the effective population size (N(e)) in the former brought about by inbreeding. However, previous analyses comparing Arabidopsis thaliana (selfer) with A. lyrata (outcrosser) have not found conclusive support for this prediction. In this study, we addressed this issue by examining silent site polymorphisms (synonymous and intronic), which are expected to be informative about changes in N(e). Two comparisons were made: A. thaliana versus A. lyrata and Capsella rubella (selfer) versus C. grandiflora (outcrosser). Extensive polymorphism data sets were obtained by compiling published data from the literature and by sequencing 354 exon loci in C. rubella and 89 additional loci in C. grandiflora. To extract information from the data effectively for studying these questions, we extended two recently developed models in order to investigate detailed selective differences between synonymous codons, mutational biases, and biased gene conversion (BGC), taking into account the effects of recent changes in population size. We found evidence that selection on synonymous codons is significantly weaker in the selfers compared with the outcrossers and that this difference cannot be fully accounted for by mutational biases or BGC.
| S-EPMC3296465 | biostudies-literature
Project description:Senecavirus A (SVA) infection was recently confirmed in pigs in Brazil, United States of America and Canada. To better understand the molecular characteristics of isolated SVA genomes, we first reported genome-wide comprehensive analyses of codon usage and various factors that have contribute to the molecular evolution in SVA. The effective number of codons (ENC) ranged from 54.51 to 55.54 with an average of 54.87 ± 0.285, which reveals a relatively stable nucleotide composition. We found that codon usage bias of the SVA was low. Mutational pressure acted as an increasingly dominant factor for the evolution of the virus compared with the natural selection. Notably, codon usage bias was also affected by the geographic distribution and isolated time. The first systemic analysis on the codon usage bias of the SVA provides important information for the understanding of the evolution of the SVA and has fundamental and theoretical benefits.
| S-EPMC7172466 | biostudies-literature
Project description:Codon usage bias is the preferential or non-random use of synonymous codons, a ubiquitous phenomenon observed in bacteria, plants and animals. Different species have consistent and characteristic codon biases. Codon bias varies not only with species, family or group within kingdom, but also between the genes within an organism. Codon usage bias has evolved through mutation, natural selection, and genetic drift in various organisms. Genome composition, GC content, expression level and length of genes, position and context of codons in the genes, recombination rates, mRNA folding, and tRNA abundance and interactions are some factors influencing codon bias. The factors shaping codon bias may also be involved in evolution of the universal genetic code. Codon-usage bias is critical factor determining gene expression and cellular function by influencing diverse processes such as RNA processing, protein translation and protein folding. Codon usage bias reflects the origin, mutation patterns and evolution of the species or genes. Investigations of codon bias patterns in genomes can reveal phylogenetic relationships between organisms, horizontal gene transfers, molecular evolution of genes and identify selective forces that drive their evolution. Most important application of codon bias analysis is in the design of transgenes, to increase gene expression levels through codon optimization, for development of transgenic crops. The review gives an overview of deviations of genetic code, factors influencing codon usage or bias, codon usage bias of nuclear and organellar genes, computational methods to determine codon usage and the significance as well as applications of codon usage analysis in biological research, with emphasis on plants.
| S-EPMC8613526 | biostudies-literature
Project description:BackgroundThe influenza A virus is an important infectious cause of morbidity and mortality in humans and was responsible for 3 pandemics in the 20th century. As the replication of the influenza virus is based on its host's machinery, codon usage of its viral genes might be subject to host selection pressures, especially after interspecies transmission. A better understanding of viral evolution and host adaptive responses might help control this disease.ResultsRelative Synonymous Codon Usage (RSCU) values of the genes from segment 1 to segment 6 of avian and human influenza viruses, including pandemic H1N1, were studied via Correspondence Analysis (CA). The codon usage patterns of seasonal human influenza viruses were distinct among their subtypes and different from those of avian viruses. Newly isolated viruses could be added to the CA results, creating a tool to investigate the host origin and evolution of viral genes. It was found that the 1918 pandemic H1N1 virus contained genes with mammalian-like viral codon usage patterns, indicating that the introduction of this virus to humans was not through in toto transfer of an avian influenza virus.Many human viral genes had directional changes in codon usage over time of viral isolation, indicating the effect of host selection pressures. These changes reduced the overall GC content and the usage of G at the third codon position in the viral genome. Limited evidence of translational selection pressure was found in a few viral genes.ConclusionsCodon usage patterns from CA allowed identification of host origin and evolutionary trends in influenza viruses, providing an alternative method and a tool to understand the evolution of influenza viruses. Human influenza viruses are subject to selection pressure on codon usage which might assist in understanding the characteristics of newly emerging viruses.
| S-EPMC2933640 | biostudies-literature
Project description:Alternative synonymous codons are often used at unequal frequencies. Classically, studies of such codon usage bias (CUB) attempted to separate the impact of neutral from selective forces by assuming that deviations from a predicted neutral equilibrium capture selection. However, GC-biased gene conversion (gBGC) can also cause deviation from a neutral null. Alternatively, selection has been inferred from CUB in highly expressed genes, but the accuracy of this approach has not been extensively tested, and gBGC can interfere with such extrapolations (e.g., if expression and gene conversion rates covary). It is therefore critical to examine deviations from a mutational null in a species with no gBGC. To achieve this goal, we implement such an analysis in the highly AT rich genome of Dictyostelium discoideum, where we find no evidence of gBGC. We infer neutral CUB under mutational equilibrium to quantify "adaptive codon preference," a nontautologous genome wide quantitative measure of the relative selection strength driving CUB. We observe signatures of purifying selection consistent with selection favoring adaptive codon preference. Preferred codons are not GC rich, underscoring the independence from gBGC. Expression-associated "preference" largely matches adaptive codon preference but does not wholly capture the influence of selection shaping patterns across all genes, suggesting selective constraints associated specifically with high expression. We observe patterns consistent with effects on mRNA translation and stability shaping adaptive codon preference. Thus, our approach to quantifying adaptive codon preference provides a framework for inferring the sources of selection that shape CUB across different contexts within the genome.
| S-EPMC8321536 | biostudies-literature
Project description:The codon usage patterns of viruses reflect the evolutionary changes that allow them to optimize their survival and adapt their fitness to the external environment and, most importantly, their hosts. Here we report the genotype-specific codon usage patterns of Zika virus (ZIKV) strains from the current and previous outbreaks. Several genotype-specific and common codon usage traits were noted in the ZIKV coding sequences, indicating their independent evolutionary origins from a common ancestor. The overall influence of natural selection was more profound than that of mutation pressure, acting on a specific set of viral genes in the Asian-genotype ZIKV strains from the recent outbreak. An interplay between codon adaptation and deoptimization may have allowed the virus to adapt to multiple host and vectors and is reported for the first time in ZIKV genomes. Combining our codon analysis with geographical data on Aedes populations in the Americas suggested that ZIKV has evolved host- and vector-specific codon usage patterns to maintain successful replication and transmission chains within multiple hosts and vectors.
| S-EPMC5117728 | biostudies-literature