scholarly journals Diversity of tRNA Clusters in the Chloroviruses

2020 ◽  
Author(s):  
Garry A. Duncan ◽  
David D. Dunigan ◽  
James L. Van Etten

ABSTRACTViruses rely on their host’s translation machinery for the synthesis of their own proteins. Problems belie viral translation when the host has a codon usage bias (CUB) that is different from an infecting virus with differences in the GC content between the host/virus genome. Here, we evaluate the hypothesis that chloroviruses adapted to host CUB by acquisition and selection of tRNAs that at least partially favor their own CUB. The genomes of 41 chloroviruses comprising three clades of three different algal hosts have been sequenced, assembled and annotated. All 41 viruses not only encode tRNAs, but their tRNA genes are located in clusters. One tRNA gene was common to all three clades of chloroviruses, while differences were observed between clades and even within clades. By comparing the codon usage of one chlorovirus algal host, whose genome has been sequenced and annotated (67% GC content), to that of two of its viruses (40% GC content), we found that the viruses were able to at least partially overcome the host’s CUB by encoding tRNAs that recognize AU-rich codons. In addition, 39/41 chloroviruses encode a putative lysidine synthase, which alters the anticodon of tRNAmet that normally recognizes AUG to recognize the codon AUA, a codon for isoleucine. This is advantageous to the viruses because the AU-rich codon AUA is 12-13 times more common in the chloroviruses than their host. Evidence is presented that supports the concept that chlorovirus tRNA clusters were acquired prior to events that separated them into the three clades.IMPORTANCEChloroviruses are members of a group of giant viruses that infect freshwater green algae around the world. More than 40 chloroviruses have been sequenced and annotated. In order to propagate efficiently, chloroviruses with low GC content must overcome the high GC content and codon usage bias (CUB) of their hosts. We provide support for one mechanism by which viruses can overcome host CUB. Specifically, the chloroviruses examined herein encode tRNAs whose cognate codons are common in the viruses but not in the host. Virus-encoded tRNAs that recognize AU-rich codons enable more efficient protein synthesis, thus enhancing viral propagation. The tRNA genes are located in clusters and the original tRNA gene cluster was acquired by the most recent common ancestor of the four chlorovirus clades. Furthermore, we show some conservation among all clades, but also substantial variation between and within clades, demonstrating the dynamics of viral evolution.

Viruses ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 1173
Author(s):  
Garry A. Duncan ◽  
David D. Dunigan ◽  
James L. Van Etten

Viruses rely on their host’s translation machinery for the synthesis of their own proteins. Problems belie viral translation when the host has a codon usage bias (CUB) that is different from an infecting virus due to differences in the GC content between the host and virus genomes. Here, we examine the hypothesis that chloroviruses adapted to host CUB by acquisition and selection of tRNAs that at least partially favor their own CUB. The genomes of 41 chloroviruses comprising three clades, each infecting a different algal host, have been sequenced, assembled and annotated. All 41 viruses not only encode tRNAs, but their tRNA genes are located in clusters. While differences were observed between clades and even within clades, seven tRNA genes were common to all three clades of chloroviruses, including the tRNAArg gene, which was found in all 41 chloroviruses. By comparing the codon usage of one chlorovirus algal host, in which the genome has been sequenced and annotated (67% GC content), to that of two of its viruses (40% GC content), we found that the viruses were able to at least partially overcome the host’s CUB by encoding tRNAs that recognize AU-rich codons. Evidence presented herein supports the hypothesis that a chlorovirus tRNA cluster was present in the most recent common ancestor (MRCA) prior to divergence into three clades. In addition, the MRCA encoded a putative isoleucine lysidine synthase (TilS) that remains in 39/41 chloroviruses examined herein, suggesting a strong evolutionary pressure to retain the gene. TilS alters the anticodon of tRNAMet that normally recognizes AUG to then recognize AUA, a codon for isoleucine. This is advantageous to the chloroviruses because the AUA codon is 12–13 times more common in the chloroviruses than their host, further helping the chloroviruses to overcome CUB. Among large DNA viruses infecting eukaryotes, the presence of tRNA genes and tRNA clusters appear to be most common in the Phycodnaviridae and, to a lesser extent, in the Mimiviridae.


2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Himangshu Deka ◽  
Supriyo Chakraborty

It is vital to unravel the codon usage bias in order to gain insights into the evolutionary forces dictating the viral evolution process. InfluenzaAvirus has attracted attention of many investigators over the years due to high mutation rate and being cross-specific shift operational in the viral genome. Several authors have reported that the codon usage bias is low in influenzaAviruses, citing mutational pressure as the decisive force shaping up the codon usage in these viruses. In this study, complete coding sequences of hemagglutinin genes for H1N1 subtype of influenzaAvirus have been explored for the possible codon usage bias acting upon these genes. The results indicate overall low bias with peaking ENC values. The GC content is found to be substantially low as against AT content in the silent codon sites. Significant correlations were observed in between the compositional parameters versus AT3, implying the possible role of the latter in shaping codon usage profile in the viral hemagglutinin. The data showed conspicuously that the sequences wereAredundant with most codons preferring nucleotideAover others in the third synonymous codon site. The results indicated the pivotal role of compositional pressure affecting codon usage in this virus.


2021 ◽  
Author(s):  
Neetu Tyagi ◽  
Rahila Sardar ◽  
Dinesh Gupta

AbstractThe Coronavirus disease 2019 (COVID-19) outbreak caused by Severe Acute Respiratory Syndrome Coronavirus 2 virus (SARS-CoV-2) poses a worldwide human health crisis, causing respiratory illness with a high mortality rate. To investigate the factors governing codon usage bias in all the respiratory viruses, including SARS-CoV-2 isolates from different geographical locations (~62K), including two recently emerging strains from the United Kingdom (UK), i.e., VUI202012/01 and South Africa (SA), i.e., 501.Y.V2 codon usage bias (CUBs) analysis was performed. The analysis includes RSCU analysis, GC content calculation, ENC analysis, dinucleotide frequency and neutrality plot analysis. We were motivated to conduct the study to fulfil two primary aims: first, to identify the difference in codon usage bias amongst all SARS-CoV-2 genomes and, secondly, to compare their CUBs properties with other respiratory viruses. A biased nucleotide composition was found as most of the highly preferred codons were A/U-ending in all the respiratory viruses studied here. Compared with the human host, the RSCU analysis led to the identification of 11 over-represented codons and 9 under-represented codons in SARS-CoV-2 genomes. Correlation analysis of ENC and GC3s revealed that mutational pressure is the leading force determining the CUBs. The present study results yield a better understanding of codon usage preferences for SARS-CoV-2 genomes and discover the possible evolutionary determinants responsible for the biases found among the respiratory viruses, thus unveils a unique feature of the SARS-CoV-2 evolution and adaptation. To the best of our knowledge, this is the first attempt at comparative CUBs analysis on the worldwide genomes of SARS-CoV-2, including novel emerged strains and other respiratory viruses.


mBio ◽  
2014 ◽  
Vol 5 (2) ◽  
Author(s):  
Wenqi Ran ◽  
David M. Kristensen ◽  
Eugene V. Koonin

ABSTRACT The relationship between the selection affecting codon usage and selection on protein sequences of orthologous genes in diverse groups of bacteria and archaea was examined by using the Alignable Tight Genome Clusters database of prokaryote genomes. The codon usage bias is generally low, with 57.5% of the gene-specific optimal codon frequencies (F opt ) being below 0.55. This apparent weak selection on codon usage contrasts with the strong purifying selection on amino acid sequences, with 65.8% of the gene-specific dN/dS ratios being below 0.1. For most of the genomes compared, a limited but statistically significant negative correlation between F opt and dN/dS was observed, which is indicative of a link between selection on protein sequence and selection on codon usage. The strength of the coupling between the protein level selection and codon usage bias showed a strong positive correlation with the genomic GC content. Combined with previous observations on the selection for GC-rich codons in bacteria and archaea with GC-rich genomes, these findings suggest that selection for translational fine-tuning could be an important factor in microbial evolution that drives the evolution of genome GC content away from mutational equilibrium. This type of selection is particularly pronounced in slowly evolving, “high-status” genes. A significantly stronger link between the two aspects of selection is observed in free-living bacteria than in parasitic bacteria and in genes encoding metabolic enzymes and transporters than in informational genes. These differences might reflect the special importance of translational fine-tuning for the adaptability of gene expression to environmental changes. The results of this work establish the coupling between protein level selection and selection for translational optimization as a distinct and potentially important factor in microbial evolution. IMPORTANCE Selection affects the evolution of microbial genomes at many levels, including both the structure of proteins and the regulation of their production. Here we demonstrate the coupling between the selection on protein sequences and the optimization of codon usage in a broad range of bacteria and archaea. The strength of this coupling varies over a wide range and strongly and positively correlates with the genomic GC content. The cause(s) of the evolution of high GC content is a long-standing open question, given the universal mutational bias toward AT. We propose that optimization of codon usage could be one of the key factors that determine the evolution of GC-rich genomes. This work establishes the coupling between selection at the level of protein sequence and at the level of codon choice optimization as a distinct aspect of genome evolution.


2018 ◽  
Vol 15 (138) ◽  
pp. 20170667 ◽  
Author(s):  
Sophia S. Liu ◽  
Adam J. Hockenberry ◽  
Michael C. Jewett ◽  
Luís A. N. Amaral

The unequal utilization of synonymous codons affects numerous cellular processes including translation rates, protein folding and mRNA degradation. In order to understand the biological impact of variable codon usage bias (CUB) between genes and genomes, it is crucial to be able to accurately measure CUB for a given sequence. A large number of metrics have been developed for this purpose, but there is currently no way of systematically testing the accuracy of individual metrics or knowing whether metrics provide consistent results. This lack of standardization can result in false-positive and false-negative findings if underpowered or inaccurate metrics are applied as tools for discovery. Here, we show that the choice of CUB metric impacts both the significance and measured effect sizes in numerous empirical datasets, raising questions about the generality of findings in published research. To bring about standardization, we developed a novel method to create synthetic protein-coding DNA sequences according to different models of codon usage. We use these benchmark sequences to identify the most accurate and robust metrics with regard to sequence length, GC content and amino acid heterogeneity. Finally, we show how our benchmark can aid the development of new metrics by providing feedback on its performance compared to the state of the art.


2021 ◽  
Author(s):  
Zhihua Ou ◽  
Wei Liu ◽  
Junhua LI ◽  
Hongli Du

Human papillomavirus type 16 (HPV16) is the most prevalent HPV type causing cervical cancers. Herein, using 1,597 full genomes of HPV16, we systemically investigated the mutation profiles, surface protein glycosylation sites and the codon usage bias of the eight open reading frames (ORFs) of HPV16 genomes from different lineages and sublineages. Multiple lineage- or subline-age-specific mutation sites were identified. Glycosylation analysis showed that HPV16 lineage D contained the highest number of unique potential glycosylation site in both L1 and L2 capsid protein, which might lead to their antigenic distances from other HPV16 lineages. Nucleotide composition of HPV16 showed that the overall AT content was higher than GC content at the 3rd codon position. Relatively high ENC values suggested that the HPV16 ORFs didn't have strong codon usage bias. Most of the HPV16 ORFs were mainly governed by natural selection pressure such as translational pressure, except for L2. HPV16 only shared some of the preferred codons with human, which might help reduce competition in translational resources. These findings may help increase our understanding of the heterogeneity between HPV16 lineages and sublineages, and the adaptation mechanism of HPV in human cells, which might facilitate HPV classification and improve vaccine development and application.


2010 ◽  
Vol 7 (1) ◽  
pp. 131-135 ◽  
Author(s):  
Laura R. Emery ◽  
Paul M. Sharp

Patterns of codon usage have been extensively studied among Bacteria and Eukaryotes, but there has been little investigation of species from the third domain of life, the Archaea. Here, we examine the nature of codon usage bias in a methanogenic archaeon, Methanococcus maripaludis . Genome-wide patterns of codon usage are dominated by a strong A + T bias, presumably largely reflecting mutation patterns. Nevertheless, there is variation among genes in the use of a subset of putatively translationally optimal codons, which is strongly correlated with gene expression level. In comparison with Bacteria such as Escherichia coli , the strength of selected codon usage bias in highly expressed genes in M. maripaludis seems surprisingly high given its moderate growth rate. However, the pattern of selected codon usage differs between M. maripaludis and E. coli : in the archaeon, strongly selected codon usage bias is largely restricted to twofold degenerate amino acids (AAs). Weaker bias among the codons for fourfold degenerate AAs is consistent with the small number of tRNA genes in the M. maripaludis genome.


2010 ◽  
Vol 19 ◽  
pp. 49-58 ◽  
Author(s):  
S. K. Behura ◽  
M. Stanke ◽  
C. A. Desjardins ◽  
J. H. Werren ◽  
D. W. Severson

2017 ◽  
Author(s):  
Prashant Mainali ◽  
Sobita Pathak

ABSTRACTCodon usage bias is the preferential use of the subset of synonymous codons during translation. In this paper, the comparisons of normalized entropy and GC content between the sequence of coding regions of Escherichia coli k12 and noncoding regions (ncRNA, rRNA) of various organisms were done to shed light on the origin of the codon usage bias.The normalized entropy of the coding regions was found significantly higher than the noncoding regions, suggesting the role of the translation process in shaping codon usage bias. Further, when the position specific GC content of both coding and noncoding regions was analyzed, the GC2 content in coding regions was lower than GC1 and GC2 while in noncoding regions, the GC1, GC2, GC3 contents were approximately equal. This discrepancy is explained by the biased mutation coupled with the presence and absence of selection pressure. The accumulation of CG content occurs in the sequences due to mutation bias in DNA repair and recombination process. In noncoding regions, the mutation is harmful and thus, selected against while due to the degeneracy of codons in coding regions, a mutation in GC3 is neutral and hence, not selected. Thus, the accumulation of GC content occurs in coding regions, and thus codon usage bias occurs.


2020 ◽  
Vol 21 (11) ◽  
Author(s):  
Redi Aditama ◽  
Zulfikar Achmad Tanjung ◽  
Widyartini Made Sudania ◽  
Yogo Adhi Nugroho ◽  
Condro Utomo ◽  
...  

Abstract. Aditama R, Tanjung ZA, Sudania WM, Nugroho YA, Utomo C, Liwang T. 2020. Analysis of codon usage bias reveals optimal codons in Elaeis guineensis. Biodiversitas 21: 5331-5337. Codon usage bias of oil palm genome was reported employing several indices, including GC content, relative synonymous codon usage (RSCU), the effective number of codons (ENC), and codon adaptation index (CAI). Unimodal distribution of GC content was observed and matched with non-grass monocots characteristics. Correspondence analysis (COA) on synonymous codon usage bias showed that the main axis was strongly driven by GC content. The ENC and neutrality plot of oil palm genes indicating that natural selection played more vital role compared to mutational bias on shaping codon usage bias. A positive correlation between calculated CAI and experimental data of oil palm gene expression was detected indicating good ability of this index. Finally, eighteen codons were defined as “optimal codons” that may provide a useful reference for heterogeneous expression and genome editing studies.


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