Nucleotide Of Codon Research Articles

Investigating the Diversity and Host Range of Novel Parvoviruses from North American Ducks Using Epidemiology, Phylogenetics, Genome Structure, and Codon Usage Analysis.

Parvoviruses are small single-stranded DNA viruses that can infect both vertebrates and invertebrates. We report here the full characterization of novel viruses we identified in ducks, including two viral species within the subfamily Hamaparvovirinae (duck-associated chapparvovirus, DAC) and a novel species within the subfamily Densovirinae (duck-associated ambidensovirus, DAAD). Overall, 5.7% and 21.1% of the 123 screened ducks (American black ducks, mallards, northern pintail) were positive for DAC and DAAD, respectively, and both viruses were more frequently detected in autumn than in winter. Genome organization and predicted transcription profiles of DAC and DAAD were similar to viruses of the genera Chaphamaparvovirus and Protoambidensovirus, respectively. Their association to these genera was also demonstrated by subfamily-wide phylogenetic and distance analyses of non-structural protein NS1 sequences. While DACs were included in a highly supported clade of avian viruses, no definitive conclusions could be drawn about the host type of DAAD because it was phylogenetically close to viruses found in vertebrates and invertebrates and analyses of codon usage bias and nucleotide frequencies of viruses within the family Parvoviridae showed no clear host-based viral segregation. This study highlights the high parvoviral diversity in the avian reservoir with many avian-associated parvoviruses likely yet to be discovered.

Minimal Secondary Structure Formation on mRNAs with a Shine-Dalgarno Sequence for Chromosomal Genes in <i>Rhodobacter sphaeroides</i>

The Shine-Dalgarno (SD) sequence, when present, is known to promote translation initiation in a bacterial cell. However, the thermodynamic stability of the messenger RNA (mRNA) through its secondary structures has an inhibitory effect on the efficiency of translation. This poses the question of whether bacterial mRNAs with SD have low secondary structure formation or not. About 3500 protein-coding genes in Rhodobacter sphaeroides were analyzed and a sliding window analysis of the last 100 nucleotides of the 5’ UTR and the first 100 nucleotides of ORFs was performed using RNAfold, a software for RNA secondary structure analysis. It was shown that mRNAs with SD are less stable than those without SD for genes located on the primary chromosome, but not for the plasmid encoded genes. Furthermore, mRNA stability is similar for genes within each chromosome except those encoded by the accessory chromosome (second chromosome). Results highlight the possible contribution of other factors like replicon-specific nucleotide composition (GC content), codon bias, and protein stability in determining the efficiency of translation initiation in both SD-dependent and SD-independent translation systems.

Analysis of Codon Usage Patterns in the Human Papillomavirus Oncogenes

Background: Persistent high-risk genital human papillomavirus (HPV) infection is a major cause of cervical cancer in women. The products of the viral transforming genes E6 and E7 in the high-risk HPVs are known to be similar in their amino acid composition and structure. We performed a comparative analysis of codon usage patterns in the E6 and E7 genes of HPVs. Methods: The E6 and E7 gene sequences of eight HPV subtypes were analyzed to determine their nucleotide composition, relative synonymous codon usage (RSCU), effective number of codons (ENC), neutrality, genetic variability, selection pressure, and codon adaptation index (CAI). Additionally, a correspondence analysis (CoA) was performed. Results: The analysis to determine the effects of differences in composition on the codon usage patterns revealed that there may be usage bias for ‘A’ nucleotides. This was consistent with the results of the RSCU analysis, which demonstrated that the selection of A/T-rich patterns and the preference for A/T-ended codons in HPVs are influenced by compositional constraints. Moreover, the results reveal that selection pressure plays an important role in the CoA results for the RSCU values, Tajima’s D tests, and neutrality tests. Conclusion: The results of this study are consistent with previous findings that most papillomavirus genes are under purifying selection pressure, which limits changes to the encoded proteins. Natural selection and mutation pressures resulting in changes in the nucleotide composition and codon usage bias in the two tumor genes of HPV act differently during the evolution of the HPV subtype; thus, throughout the viral life cycle, HPV can constantly evolve to adapt to a new environment.

Isolation and molecular characterization of Fowl adenovirus strains in Black grouse: First reported case in Poland.

This article describes the isolation, molecular characterization, and genotyping of two fowl adenovirus (FAdVs) strains with GenBank Accession numbers (MT478054, JSN-G033-18-L and MT478055, JSN-G033-18-B) obtained from the internal organs of black grouse (Lyrurus tetrix). This study also reveals the first confirmation of fowl adenovirus in Poland, supporting one of the hypotheses about the probability of fowl adenovirus interspecies transmission. The adenovirus strain sequences were investigated via phylogenetic analysis and were found to have an overall mean pairwise distance of 2.189. The heterogeneity, Relative Synonymous Codon Usage (RSCU), codon composition, and nucleotide frequencies were examined. Statistical analyses and Tajima’s test for the examined sequences were carried out. The Maximum Likelihood for the examined sequences substitutions was performed. The results of the sequence analysis identified MT478054, JSN-G033-18-L and MT478055, JSN-G033-18-B as strains of fowl adenovirus 2/11/D, with the Fowl adenovirus D complete sequence showing a 93% match. Wild birds may act as a natural reservoir for FAdVs and likely play an important role in the spreading of these viruses in the environment. The findings reported here suggest horizontal transmission within and between avian species.

A retrospective cohort study of isoniazid-resistant tuberculosis treatment outcomes and isoniazid resistance-associated mutations in eastern China from 2013 to 2018

ObjectivesThe current situation of isoniazid-resistant, rifampicin-susceptible tuberculosis (Hr-TB) and associated genetic factors is not clear in China. MethodsA retrospective cohort study was conducted from 2013 to 2018 in Jiangsu Province, China. Phenotypic Hr-TB were identified by drug susceptibility testing on Lowenstein–Jensen medium and using a Mycobacterium Growth Indicator Tube 960 (MGIT 960) system, and mutations in the katG 315 codon and inhA promoter nucleotides –8, –15 and –16 were determined by GenoType MTBDRplus and sequencing. All of the Hr-TB patients enrolled were followed up until June 2019. ResultsA total of 1416 smear-positive sputum samples were collected, of which 57 were excluded due to the presence of nontuberculous mycobacteria. Finally, 63/1359 (4.6%) were determined as Hr-TB. After follow-up, 11 Hr-TB patients (17.5%) showed an unfavourable outcome, of whom 5 (7.9%) relapsed, 4 (6.3%) had treatment failure and 2 (3.2%) died. A total of 52 isolates (82.5%) were detected with either katG 315 or inhA promoter nucleotide –8, –15 or –16 mutations, whereas no canonical mutations were found in 8 isolates (12.7%); 3 isolates failed in mutation detection. TB history was found to be associated with unfavourable outcomes for Hr-TB (odds ratio = 6.13, 95% confidence interval 1.05–35.82; P = 0.04). However, mutations in katG 315 and the inhA promoter region were not found to be associated with Hr-TB unfavourable outcomes (P = 0.15). ConclusionUnfavourable outcomes for Hr-TB are serious in eastern China, especially for previously treated patients. Meanwhile, current genetic determination of Hr-TB is inadequate.

A Novel Splice-Site Mutation in MSH2 Is Associated With the Development of Lynch Syndrome.

Lynch syndrome (LS) is an inherited autosomal dominant disorder caused by germline mutations of mismatch repair (MMR) genes, including MSH2, MSH6, PMS2, and MLH1. This study aimed to analyze the molecular defects and clinical manifestations of an affected family and propose appropriate individual prevention strategies for all mutation carriers. A novel splicing mutation (c.1661+2 T>G) was identified in the MSH2 gene, which was found to co-segregate among affected family members by Whole exome sequencing (WES). RT-PCR analysis confirmed that c.1661+2 T>G could produce 3 transcripts, including 1 normal transcript and 2 aberrant transcripts. The 2 aberrant transcripts resulted in premature termination at the 6th nucleotide codon of MSH2 exon 11, so that the predicted products of the mutant MSH2 mRNAs were truncated proteins of 505 amino acids (with all of exon 10 deleted) and 528 amino acids (with a deletion of 82-nucleotides in exon 10), resulting in the loss of the interaction domain, the ATP domain and post-translationally modified residues. Quantitative RT-PCR (qRT-PCR) analysis showed that MSH2 mRNA levels in all patients were reduced to only 1/4 of the control levels. Our study reveals that a novel splicing mutation (c.1661+2 T>G) in the MSH2 gene causes LS and reaffirms the importance of genetic testing for LS.

Time series prediction of COVID-19 by mutation rate analysis using recurrent neural network-based LSTM model.

SARS-CoV-2, a novel coronavirus mostly known as COVID-19 has created a global pandemic. The world is now immobilized by this infectious RNA virus. As of June 15, already more than 7.9 million people have been infected and 432k people died. This RNA virus has the ability to do the mutation in the human body. Accurate determination of mutation rates is essential to comprehend the evolution of this virus and to determine the risk of emergent infectious disease. This study explores the mutation rate of the whole genomic sequence gathered from the patient's dataset of different countries. The collected dataset is processed to determine the nucleotide mutation and codon mutation separately. Furthermore, based on the size of the dataset, the determined mutation rate is categorized for four different regions: China, Australia, the United States, and the rest of the World. It has been found that a huge amount of Thymine (T) and Adenine (A) are mutated to other nucleotides for all regions, but codons are not frequently mutating like nucleotides. A recurrent neural network-based Long Short Term Memory (LSTM) model has been applied to predict the future mutation rate of this virus. The LSTM model gives Root Mean Square Error (RMSE) of 0.06 in testing and 0.04 in training, which is an optimized value. Using this train and testing process, the nucleotide mutation rate of 400th patient in future time has been predicted. About 0.1% increment in mutation rate is found for mutating of nucleotides from T to C and G, C to G and G to T. While a decrement of 0.1% is seen for mutating of T to A, and A to C. It is found that this model can be used to predict day basis mutation rates if more patient data is available in updated time.

Tracing Brucella evolutionary dynamics in expanding host ranges through nucleotide, codon and amino acid usages in genomes

The host range of Brucella organisms has expanded from terrestrial and marine mammals to fish and amphibians. The high homology genomes of different Brucella organisms promote us to investigate evolutionary patterns for nucleotide, codon and amino acid usage patterns at gene levels among Brucella species. Although the similar patterns for nucleotide and synonymous codon usages exist in gene population, GC composition at the first codon position has significant correlations to that of the second and third codon positions, respectively, suggesting that nucleotide usages surrounding one codon influence synonymous codon usage patterns. Evolutionary patterns represented by synonymous codon and amino acid usages reflect host factor impacting Brucella speciation. As for genetic variations of important virulent factors involved with different biological functions, genes encoding lipoplysaccharides (LPSs) display more distinctive codon adaptation to Brucella than those of the BvrR/BvrS system and type IV secretion system. By Bayesian analysis, the polygenetic constructions for these genes of virulent factors shared by Brucella species display the purifying/positive selections and partially host factor in mediating genetic variations of these genes. The systemic analyses for nucleotide, synonymous codon and amino acid usages at gene level and genetic variations of important virulent factor genes display that host limitation influences either genetic characterizations at gene level or a particular gene involved in virulent factors of Brucella. Communicated by Ramaswamy H. Sarma

Analysis of compositional properties and codon usage bias of mitochondrial CYB gene in anura, urodela and gymnophiona.

We delineated the pattern of synonymous codon usage bias (CUB) and its determinants in mitochondrial CYB gene of respiratory chain across different amphibian groups namely orders anura, urodela and gymnophiona. We observed that CUB was low in CYB gene of amphibia. The gymnophionans had comparatively high bias followed by urodeles and anurans. The codons namely TCA, CCA, CAA, CGA, TGA, AAA and ACA were over-represented in all three orders. The codons such as GCC and TCC were over-represented in anura whereas in urodela, the over-represented codons were TTA, CTA, ATA, GTA, GAA, GGA and GCA. In gymnophiona, GCC, TTA, CTA, ATA, GTA, GAA and GGA codons were over-represented. The regression analysis between effective number of codons (ENC) and nucleobase at the 3rd position revealed that nucleobase A and C influenced CUB positively in order anura, while in urodela and gymnophiona, nucleobase A and T influenced the CUB positively. Mutation pressure and natural selection mutually illustrate the CUB of CYB gene (complex III gene) of amphibia as elucidated by correlation analysis between 3rd nucleotide in a codon and overall nucleotide content of the gene. However, neutrality plot showed that natural selection was the dominant evolutionary factor of CUB.

Characterization and phylogenetic analysis of the first complete mitochondrial genome of Cylicocyclus radiatus

Cylicocyclus spp. are common parasites in the intestine of equine animals. Hosts infected by these strongylid nematodes might face emaciation, anemia, and even death, all of which lead to significant economic losses. In the present study, the complete mitochondrial genome (mitogenome) of Cylicocyclus radiatus, the type species of the genus Cylicocyclus, was sequenced and characterized for the first time using next-generation sequencing technology. Results show that the mitogenome of C. radiatus is a double-stranded 13,836 bp circular molecule, containing 12 protein-coding genes, 22 tRNA genes, two rRNA genes, and two non-coding regions. Moreover, it has a clear bias in nucleotide composition and codon preference towards protein-coding genes with elevated AT content. All protein-coding genes are initiated by ATT and TTG codons, and almost all of them end with complete TAA and TAG termination codons; only the COШ gene harbors the incomplete T termination codon. All tRNA genes fold into an atypical clover-leaf secondary structure. The tRNA-Ser genes possess a TΨC arm and variable loop, but lack the dihydrouridine arm and loop. Twenty tRNAs contain the dihydrouridine arm and loop, in which the variable TΨC arm and loop are replaced by a “TV-replacement loop”. Most tRNA gene secondary structures contain G-U, U-U, and A-G mismatches. Phylogenetic analysis based on nucleotide sequences of the 12 protein-coding genes using maximum likelihood and Bayesian inference indicated that C. radiatus is related more closely to Cylicocyclus nassatus than to Cylicocyclus insigne. In summary, this study provides the first annotated sequence of the mitogenome of C. radiatus, paving the way for further research on species classification and the molecular evolution of strongylid nematodes.

TECHNICAL ASPECTS OF LIQUID BIOPSY: INFLUENCE OF PREANALYTICAL PARAMETERS ON THE CONCENTRATION OF CIRCULATING TUMOR DNA IN PLASMA OF CANCER PATIENTS

«Liquid biopsy» is gradually becoming a mandatory procedure in cancer diagnostics. The aim of this procedure is to detect and monitor tumor-specific markers in various body fluids (blood, urine, pleural fluid, etc.). Significant efforts have been made to convert the most common mutational tests (EGFR, KRAS, BRAF) into non-invasive procedures. Despite some advantages, “liquid biopsy” is still not equivalent to traditional tissue analysis due to limited sensitivity and specificity; it cannot be routinely used in cancer medicine until the standardization of pre-analytical procedures is agreed. We intend to improve the performance of liquid biopsy for detection of a number of clinically relevant mutations (EGFR: ex19del and L858R; KRAS: 12, 13, 61, 146 codon nucleotide substitutions; BRAF: V600E). 417 plasma samples obtained from 88 patients (KRAS/NRAS/BRAF-mutated colorectal cancer (CRC): n= 57; EGFR-mutated lung adenocarcinomas (LC): n = 14; BRAF-mutated melanoma: n = 17) were analyzed by ddPCR for the presence of corresponding mutations in the circulating tumor DNA (ctDNA). Presence of tumor-specific mutations in plasma was confirmed in 32/57 (56%) CRC, 7/14 (50%) LC, and 4/17 (24%) melanoma cases. The proportion of mutation-positive plasma cases was tended to be higher in the group of patients with distant metastases compared to subjects with localized disease [34/56 (61%) vs. 5/15 (33%), р = 0.058]. 86 patients provided their blood at 9.00 (morning) and at 16.00 (afternoon). In addition, blood-takes were performed before and 15 minutes after usual breakfast as well as before and 15 minutes after moderate physical exercise. The detection rate of cancer-specific mutations in plasma was not significantly correlated with described above circumstances of blood-take. Meanwhile, the noticeable intrapatient variability of circulating mutation success rate has been detected. Thus, depending on clinical circumstances, at least negative ctDNA tests could be advised to be repeated in some patients, in order to ensure the reliability of results.

Gene transfer and nucleotide sequence evolution by Gossypium cytoplasmic genomes indicates novel evolutionary characteristics.

The DNA fragments transferred among cotton cytoplasmic genomes are highly differentiated. The wild D group cotton species have undergone much greater evolution compared with cultivated AD group. Cotton (Gossypium spp.) is one of the most economically important fiber crops worldwide. Gene transfer, nucleotide evolution, and the codon usage preferences in cytoplasmic genomes are important evolutionary characteristics of high plants. In this study, we analyzed the nucleotide sequence evolution, codon usage, and transfer of cytoplasmic DNA fragments in Gossypium chloroplast (cp) and mitochondrial (mt) genomes, including the A genome group, wild D group, and cultivated AD group of cotton species. Our analyses indicated that the differences in the length of transferred cytoplasmic DNA fragments were not significant in mitochondrial and chloroplast sequences. Analysis of the transfer of tRNAs found that trnQ and nine other tRNA genes were commonly transferred between two different cytoplasmic genomes. The Codon Adaptation Index values showed that Gossypium cp genomes prefer A/T-ending codons. Codon preference selection was higher in the D group than the other two groups. Nucleotide sequence evolution analysis showed that intergenic spacer sequences were more variable than coding regions and nonsynonymous mutations were clearly more common in cp genomes than mt genomes. Evolutionary analysis showed that the substitution rate was much higher in cp genomes than mt genomes. Interestingly, the D group cotton species have undergone much faster evolution compared with cultivated AD groups, possibly due to the selection and domestication of diverse cotton species. Our results demonstrate that gene transfer and differential nucleotide sequence evolution have occurred frequently in cotton cytoplasmic genomes.

Complete mitochondrial genome of Whitmania laevis (Annelida, Hirudinea) and comparative analyses within Whitmania mitochondrial genomes

The complete mitochondrial genome of Whitmania laevis is 14,442 bp in length and contains 37 genes including 13 protein-coding genes (PCGs), 22 transfer RNA (tRNA) genes, and two ribosomal RNA (rRNA) genes. The almost-complete mitochondrial genome of Whitmania acranulata, consisting of 13,494 bp, contains 35 genes including 13 PCGs, 20 tRNA genes, and two rRNA genes. COI phylogenetic analyses showed that the samples reported in GenBank and analysed as Hirudo nipponia KC667144, Hirudinaria manillensis KC688268 and Erpobdella octoculata KC688270 are not the named species and they should belong to Whitmania. We compared and analyzed the characteristics of nucleotide composition, codon usage, and secondary structures of 22 tRNAs and two rRNAs from Whitmania taxa. Moreover, we analyzed phylogenetic relationships of Annelida using maximum likelihood (ML) and Bayesian inference (BI) methods, based on 11 mitochondrial genes. Our results reveal that W. laevis has a close relationship with W. pigra.

Analysis of Codon Usage and Nucleotide Bias in Middle East Respiratory Syndrome Coronavirus Genes

The Middle East Respiratory Syndrome (MERS) is an emerging disease caused by a recently identified human coronavirus (CoV). Over 2494 laboratory-confirmed cases and 858 MERS-related deaths have been reported from 27 countries. MERS-CoV has been associated with a high case fatality rate, especially in patients with pre-existing conditions. Despite the fatal nature of MERS-CoV infection, a comprehensive study to explore its evolution and adaptation in different hosts is lacking. We performed codon usage analyses on 4751 MERS-CoV genes and determined underlying forces that affect the codon usage bias in the MERS-CoV genome. The current analyses revealed a low but highly conserved, gene-specific codon usage bias in the MERS-CoV genome. The codon usage bias is mainly shaped by natural selection, while mutational pressure emerged as a minor factor affecting codon usage in some genes. Other contributory factors included CpG dinucleotide bias, physical and chemical properties of encoded proteins and gene length. Results reported in this study provide considerable insights into the molecular evaluation of MERS-CoV and could serve as a theoretical basis for optimizing MERS-CoV gene expression to study the functional relevance of various MERS-CoV proteins. Alternatively, an attenuated vaccine strain containing hundreds of silent mutations could be engineered. Codon de-optimization will not affect the amino acid sequence or antigenicity of a vaccine strain, but the sheer number of mutations would make viral reversion to a virulent phenotype extremely unlikely.

CodonAdjust: a software for in silico design of a mutagenesis library with specific amino acid profiles.

In protein engineering, generation of mutagenesis libraries is a key step to study the functions of mutants. To generate mutants with a desired composition of amino acids (AAs), a codon consisting of a mixture of nucleotides is widely applied. Several computational methods have been proposed to calculate a codon nucleotide composition for generating a given amino acid profile based on mathematical optimization. However, these previous methods need to manually tune weights of amino acids in objective functions, which are time-consuming and, more importantly, lack publicly available software implementations. Here, we develop CodonAdjust, a software to adjust a codon nucleotide composition for mimicking a given amino acid profile. We propose different options of CodonAdjust, which provide various customizations in practical scenarios such as setting a guaranteeing threshold for the frequencies of amino acids without any manual tasks. We demonstrate the capability of CodonAdjust in the experiments on the complementarity-determining regions (CDRs) of antibodies and T-cell receptors (TCRs) as well as millions of amino acid profiles from Pfam. These results suggest that CodonAdjust is a productive software for codon design and may accelerate library generation. CodonAdjust is freely available at https://github.com/tiffany-nguyen/CodonAdjust. Paper edited by Dr. Jeffery Saven, Board Member for PEDS.

Codon Usage in the Iflaviridae Family Is Not Diverse Though the Family Members Are Isolated from Diverse Host Taxa.

All iflavirus members belong to the unique genus, Iflavirus, of the family, Iflaviridae. The host taxa and sequence identities of these viruses are diverse. A codon usage bias, maintained by a balance between selection, mutation, and genetic drift, exists in a wide variety of organisms. We characterized the codon usage patterns of 44 iflavirus genomes that were isolated from the classes, Insecta, Arachnida, Mammalia, and Malacostraca. Iflaviruses lack a strong codon usage bias when they are evaluated using an effective number of codons. The odds ratios of the majority of dinucleotides are within the normal range. However, the dinucleotides at the 1st–2nd codon positions are more biased than those at the 2nd–3rd codon positions. Plots of effective numbers of codons, relative neutrality analysis, and PR2 bias analysis all indicate that selection pressure dominates mutations in shaping codon usage patterns in the family, Iflaviridae. When these viruses were grouped into their host taxa, we found that the indices, including the nucleotide composition, effective number of codons, relative synonymous codon usage, and the influencing factors behind the codon usage patterns, all show that there are non-significant differences between the six host-taxa-groups. Our results disagree with our assumption that diverse viruses should possess diverse codon usage patterns, suggesting that the nucleotide composition and codon usage in the family, Iflaviridae, are not host taxa-specific signatures.

Comparative genomics of hepatitis A virus, hepatitis C virus, and hepatitis E virus provides insights into the evolutionary history of Hepatovirus species.

The intraspecies genomic diversity of the single‐strand RNA (+) virus species hepatitis A virus (Hepatovirus), hepatitis C virus (Hepacivirus), and hepatitis E virus (Orthohepevirus) was compared. These viral species all can cause liver inflammation (hepatitis), but share no gene similarity. The codon usage of human hepatitis A virus (HAV) is suboptimal for replication in its host, a characteristic it shares with taxonomically related rodent, simian, and bat hepatitis A virus species. We found this codon usage to be strikingly similar to that of Triatoma virus that infects blood‐sucking kissing bugs. The codon usage of that virus is well adapted to its insect host. The codon usage of HAV is also similar to other invertebrate viruses of various taxonomic families. An evolutionary ancestor of HAV and related virus species is hypothesized to be an insect virus that underwent a host jump to infect mammals. The similarity between HAV and invertebrate viruses goes beyond codon usage, as they also share amino acid composition characteristics, while not sharing direct sequence homology. In contrast, hepatitis C virus and hepatitis E virus are highly similar in codon usage preference, nucleotide composition, and amino acid composition, and share these characteristics with Human pegivirus A, West Nile virus, and Zika virus. We present evidence that these observations are only partly explained by differences in nucleotide composition of the complete viral codon regions. We consider the combination of nucleotide composition, amino acid composition, and codon usage preference suitable to provide information on possible evolutionary similarities between distant virus species that cannot be investigated by phylogeny.

Nucleotide composition and synonymous codon usage of open reading frames in Norovirus GII.4 variants

Norovirus GII.4 variants, a genotype in genogroup II belonging to the genus Norovirus, is a single-strand positive sense RNA containing three open reading frames (ORF1, ORF2 and ORF3) and is the most important pathogen causing nonbacterial gastroenteritis outbreaks. By using bioinformatic softwares such as Codon W, SPSS and so on, a total of 292 strains of the viruses isolated from 1974 to 2016 were analyzed for nucleotide composition and synonymous codon usage in each ORF. The result shows that it is enriched for A over the other bases in nucleotide composition, G behind the other bases in the 3rd site of all synonymous codons in the three ORFs. The patterns of nucleotide composition and codon bias of ORF2 are similar to those of ORF3 and different from those of ORF1. There are generally UpA motif and CpG motif in the codons with the lowest proportion. Correspondence analysis indicates that the codon usage may be changing over a certain time period for ORF1 in 2006 and 2012, ORF2 in 2012, and ORF3 in 2013. ENC (effective number of codons) plot and other analyses indicate that both natural selection and mutational pressure play partly roles in the ORFs, but natural selection is more important for ORF2 and ORF3. Besides, we also found all optimal codons in the ORFs. The study provides a basic understanding of the mechanism for norovirus GII.4 codon usage bias. AbbreviationsORFOpen Reading FrameENCEffective Number of CodonsCOAcorrespondence analysisRSCURelative Synonymous Codon UsageCAICodon Adaptation IndexCBICodon Bias IndexFopfrequency of optimal codonsL_symnumber of synonymous codonsL_aalength amino acidsGRAVYgrand average of hydropathicityAromaaromaticityCommunicated by Ramaswamy H. Sarma

Insights into the nucleotide composition and codon usage pattern of human tumor suppressor genes.

Tumor suppressor genes encode different proteins that inhibit the uncontrolled proliferation of cell growth and tumor development. To acquire clues for predicting gene expression level, it is essential to understand the codon usage bias (CUB) of genes to characterize genome which possesses its own compositional characteristics and unique coding sequences. We used bioinformatic tools to analyze the codon usage patterns of 637 human tumor suppressor genes as no work was reported earlier. The mean effective number of codons of these genes was 48, indicating low CUB. Our results exhibited a significant positive correlation among different nucleotide compositions and the codons ending with C base was most frequently used along with the most over-represented codon CTG and GTG codifying leucine and valine amino acid, respectively, in human tumor suppressor genes. The neutrality plot showed a significant positive correlation (Pearson, r = 0. 646; P < .01) suggesting that mutation on GC bias might affect the CUB. However, the linear regression coefficient of GC12 on GC3 in human tumor suppressor genes suggested that natural selection played a major role while mutation pressure played a minor role in the codon usage patterns of tumor suppressor genes in human. Our study would throw light into the factors that affect CUB and the codon usage patterns in the human tumor suppressor genes.

Comparative mitogenomics of the Decapoda reveals evolutionary heterogeneity in architecture and composition

The emergence of cost-effective and rapid sequencing approaches has resulted in an exponential rise in the number of mitogenomes on public databases in recent years, providing greater opportunity for undertaking large-scale comparative genomic and systematic research. Nonetheless, current datasets predominately come from small and disconnected studies on a limited number of related species, introducing sampling biases and impeding research of broad taxonomic relevance. This study contributes 21 crustacean mitogenomes from several under-represented decapod infraorders including Polychelida and Stenopodidea, which are used in combination with 225 mitogenomes available on NCBI to investigate decapod mitogenome diversity and phylogeny. An overview of mitochondrial gene orders (MGOs) reveals a high level of genomic variability within the Decapoda, with a large number of MGOs deviating from the ancestral arthropod ground pattern and unevenly distributed among infraorders. Despite the substantial morphological and ecological variation among decapods, there was limited evidence for correlations between gene rearrangement events and species ecology or lineage specific nucleotide substitution rates. Within a phylogenetic context, predicted scenarios of rearrangements show some MGOs to be informative synapomorphies for some taxonomic groups providing strong independent support for phylogenetic relationships. Additional comparisons for a range of mitogenomic features including nucleotide composition, strand asymmetry, unassigned regions and codon usage indicate several clade-specific trends that are of evolutionary and ecological interest.