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BACKGROUND: Viral diseases of sweet potatoes are causing severe crop losses worldwide. More than 30 viruses have been identified to infect sweet potatoes among which the sweet potato latent virus (SPLV), sweet potato mild speckling virus (SPMSV), sweet potato virus G (SPVG) and sweet potato virus 2 (SPV2) have been recognized as distinct species of the genus Potyvirus in the family Potyviridae. The sweet potato virus 2 (SPV2) is a primary pathogen affecting sweet potato crops. METHODS: In this study, we detected an SPV2 isolate (named SPV2-LN) in Ipomoea nil in China. The complete genomic sequence of SPV2-LN was obtained using sequencing of small RNAs, RT-PCR, and RACE amplification. The codon usage, phylogeny, recombination analysis and selective pressure analysis were assessed on the SPV2-LN genome. RESULTS: The complete genome of SPV2-LN consisted of 10,606 nt (GenBank No. OR842902), encoding 3425 amino acids. There were 28 codons in the SPV2-LN genome with a relative synonymous codon usage (RSCU) value greater than 1, of which 21 end in A/U. Among the 12 proteins of SPV2, P3 and P3N-PIPO exhibited the highest variability in their amino acid sequences, while P1 was the most conserved, with an amino acid sequence identity of 87-95.3%. The phylogenetic analysis showed that 21 SPV2 isolates were clustered into four groups, and SPV2-LN was clustered together with isolate yu-17-47 (MK778808) in group IV. Recombination analysis indicated no major recombination sites in SPV2-LN. Selective pressure analysis showed dN/dS of the 12 proteins of SPV2 were less than 1, indicating that all were undergoing negative selection, except for P1N-PISPO. CONCLUSION: This study identified a sweet potato virus, SPV2-LN, in Ipomoea nil. Sequence identities and genome analysis showed high similarity between our isolate and a Chinese isolate, yu-17-47, isolated from sweet potato. These results will provide a theoretical basis for understanding the genetic evolution and viral spread of SPV2.

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To predict potential epidemic outbreaks, we tested our strategy, Epi-Clock, which applies the novel ZHU algorithm to different SARS-CoV-2 datasets before outbreaks to search for significant mutational accumulation patterns correlated with outbreak events. Surprisingly, some inter-species genetic distances in Coronaviridae may represent intermediate states of different species or subspecies in the evolutionary history of Coronaviridae. The insertions and deletions in whole-genome sequences between different hosts were separately associated with important roles in host transmission and shifts in Coronaviridae. Furthermore, we believe that non-nucleosomal DNA may play a dominant role in the divergence of different lineages of SARS-CoV-2 in different regions of the world owing to the lack of nucleosome protection. We suggest that strong selective variation among different lineages of SARS-CoV-2 is required to produce strong codon usage bias, which appears in B.1.640.2 and B.1.617.2 (Delta). Notably, we found that an increasing number of other types of substitutions, such as those resulting from the hitchhiking effect, accumulated, especially in the pre-breakout phase, although some of the previous substitutions were replaced by other dominant genotypes. From most validations, we could accurately predict the potential pre-phase of outbreaks with a median interval of 5 days.

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BACKGROUND: The global spread of the plasmid-mediated mcr (mobilized colistin resistance) gene family presents a significant threat to the efficacy of colistin, a last-line defense against numerous Gram-negative pathogens. The mcr-9 is the second most prevalent variant after mcr-1. METHODS: A dataset of 698 mcr-9-positive isolates from 44 countries is compiled. The historical trajectory of the mcr-9 gene is reconstructed using Bayesian analysis. The effective reproduction number is used innovatively to study the transmission dynamics of this mobile-drug-resistant gene. FINDINGS: Our investigation traces the origins of mcr-9 back to the 1960s, revealing a subsequent expansion from Western Europe to the America and East Asia in the late 20th century. Currently, its transmissibility remains high in Western Europe. Intriguingly, mcr-9 likely emerged from human-associated Salmonella and exhibits a unique propensity for transmission within the Enterobacter. Our research provides a new perspective that this host preference may be driven by codon usage biases in plasmids. Specifically, mcr-9-carrying plasmids prefer the nucleotide C over T compared to mcr-1-carrying plasmids among synonymous codons. The same bias is seen in Enterobacter compared to Escherichia (respectively as their most dominant genus). Furthermore, we uncovered fascinating patterns of coexistence between different mcr-9 subtypes and other resistance genes. Characterized by its low colistin resistance, mcr-9 has used this seemingly benign feature to silently circumnavigate the globe, evading conventional detection methods. However, colistin-resistant Enterobacter strains with high mcr-9 expression have emerged clinically, implying a strong risk of mcr-9 evolving into a global "true-resistance-gene". INTERPRETATION: This study explores the mcr-9 gene, emphasizing its origin, adaptability, and dissemination potential. Given the high mcr-9 expression colistin-resistant strains was observed in clinically the prevalence of mcr-9 poses a significant challenge to drug resistance prevention and control within the One Health framework. FUNDING: This work was partially supported by the National Natural Science Foundation of China (Grant No. 32141001 and 81991533).

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While bioactivity and a favorable safety profile for biotherapeutics is of utmost importance, manufacturability is also worth of consideration to ease the manufacturing process. Manufacturability in the scientific literature is mostly related to stability of formulated drug substances, with limited focus on downstream process-related manufacturability, that is, how easily can a protein be purified. Process-related impurities or biological impurities like viruses and host cell proteins (HCP) are present in the harvest which have mostly acid isoelectric points and need to be removed to ensure patient safety. Therefore, during molecule design, the surface charge of the target molecule should preferably differ sufficiently from the surface charge of the impurities to enable an efficient purification strategy. In this feasibility study, we evaluated the possibility of improving manufacturability by adapting the surface charge of the target protein. We generated several variants of a GLP1-receptor-agonist-Fc-domain-FGF21-fusion protein and demonstrated proof of concept exemplarily for an anion exchange chromatography step which then can be operated at high pH values with maximal product recovery allowing removal of HCP and viruses. Altering the surface charge distribution of biotherapeutic proteins can thus be useful allowing for an efficient manufacturing process for removing HCP and viruses, thereby reducing manufacturing costs.

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Tomato brown rugose fruit virus (ToBRFV) poses a significant threat to tomato production worldwide, prompting extensive research into its genetic diversity, evolutionary dynamics, and adaptive strategies. In this study, we conducted a comprehensive analysis of ToBRFV at the codon level, focusing on codon usage bias, selection pressures, and evolutionary patterns across multiple genes. Our analysis revealed distinct patterns of codon usage bias and selection pressures within the ToBRFV genome, with varying levels of genetic diversity and evolutionary constraints among different genes. We observed a transition/transversion bias of 2.07 across the entire ToBRFV genome, with the movement protein (MP) gene exhibiting the highest transition/transversion bias and SNP density, suggesting potential evolutionary pressures or a higher mutation rate in this gene. Furthermore, our study identified episodic positive selection primarily in the MP gene, highlighting specific codons subject to adaptive changes in response to host immune pressures or environmental factors. Comparative analysis of codon usage bias in the coat protein (CP) and RNA-dependent RNA polymerase (RdRp) genes revealed gene-specific patterns reflecting functional constraints and adaptation to the host's translational machinery. Our findings provide valuable insights into the molecular mechanisms driving ToBRFV evolution and adaptation, with implications for understanding viral pathogenesis, host-virus interactions, and the development of control strategies. Future research directions include further elucidating the functional significance of codon usage biases, exploring the role of episodic positive selection in viral adaptation, and leveraging these insights to inform the development of effective antiviral strategies and crop protection measures.

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The nearly neutral theory of molecular evolution posits variation among species in the effectiveness of selection. In an idealized model, the census population size determines both this minimum magnitude of the selection coefficient required for deleterious variants to be reliably purged, and the amount of neutral diversity. Empirically, an 'effective population size' is often estimated from the amount of putatively neutral genetic diversity and is assumed to also capture a species' effectiveness of selection. A potentially more direct measure of the effectiveness of selection is the degree to which selection maintains preferred codons. However, past metrics that compare codon bias across species are confounded by among-species variation in %GC content and/or amino acid composition. Here, we propose a new Codon Adaptation Index of Species (CAIS), based on Kullback-Leibler divergence, that corrects for both confounders. We demonstrate the use of CAIS correlations, as well as the Effective Number of Codons, to show that the protein domains of more highly adapted vertebrate species evolve higher intrinsic structural disorder.

Evolution is the process through which populations change over time, starting with mutations in the genetic sequence of an organism. Many of these mutations harm the survival and reproduction of an organism, but only by a very small amount. Some species, especially those with large populations, can purge these slightly harmful mutations more effectively than other species. This fact has been used by the 'drift barrier theory' to explain various profound differences amongst species, including differences in biological complexity. In this theory, the effectiveness of eliminating slightly harmful mutations is specified by an 'effective' population size, which depends on factors beyond just the number of individuals in the population. Effective population size is normally calculated from the amount of time a 'neutral' mutation (one with no effect at all) stays in the population before becoming lost or taking over. Estimating this time requires both representative data for genetic diversity and knowledge of the mutation rate. A major limitation is that these data are unavailable for most species. A second limitation is that a brief, temporary reduction in the number of individuals has an oversized impact on the metric, relative to its impact on the number of slighly harmful mutations accumulated. Weibel, Wheeler et al. developed a new metric to more directly determine how effectively a species purges slightly harmful mutations. Their approach is based on the fact that the genetic code has 'synonymous' sequences. These sequences code for the same amino acid building block, with one of these sequences being only slightly preferred over others. The metric by Weibel, Wheeler et al. quantifies the proportion of the genome from which less preferred synonymous sequences have been effectively purged. It judges a population to have a higher effective population size when the usage of synonymous sequences departs further from the usage predicted from mutational processes. The researchers expected that natural selection would favour 'ordered' proteins with robust three-dimensional structures, i.e., that species with a higher effective population size would tend to have more ordered versions of a protein. Instead, they found the opposite: species with a higher effective population size tend to have more disordered versions of the same protein. This changes our view of how natural selection acts on proteins. Why species are so different remains a fundamental question in biology. Weibel, Wheeler et al. provide a useful tool for future applications of drift barrier theory to a broad range of ways that species differ.

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Mouse (Mus musculus) models have been heavily utilized in developmental biology research to understand mammalian embryonic development, as mice share many genetic, physiological, and developmental characteristics with humans. New explorations into the integration of temporal (stage-specific) and transcriptional (tissue-specific) data have expanded our knowledge of mouse embryo tissue-specific gene functions. To better understand the substantial impact of synonymous mutational variations in the cell-state-specific transcriptome on a tissue's codon and codon pair usage landscape, we have established a novel resource-Mouse Embryo Codon and Codon Pair Usage Tables (Mouse Embryo CoCoPUTs). This webpage not only offers codon and codon pair usage, but also GC, dinucleotide, and junction dinucleotide usage, encompassing four strains, 15 murine embryonic tissue groups, 18 Theiler stages, and 26 embryonic days. Here, we leverage Mouse Embryo CoCoPUTs and employ the use of heatmaps to depict usage changes over time and a comparison to human usage for each strain and embryonic time point, highlighting unique differences and similarities. The usage similarities found between mouse and human central nervous system data highlight the translation for projects leveraging mouse models. Data for this analysis can be directly retrieved from Mouse Embryo CoCoPUTs. This cutting-edge resource plays a crucial role in deciphering the complex interplay between usage patterns and embryonic development, offering valuable insights into variation across diverse tissues, strains, and stages. Its applications extend across multiple domains, with notable advantages for biotherapeutic development, where optimizing codon usage can enhance protein expression; one can compare strains, tissues, and mouse embryonic stages in one query. Additionally, Mouse Embryo CoCoPUTs holds great potential in the field of tissue-specific genetic engineering, providing insights for tailoring gene expression to specific tissues for targeted interventions. Furthermore, this resource may enhance our understanding of the nuanced connections between usage biases and tissue-specific gene function, contributing to the development of more accurate predictive models for genetic disorders.

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Monogeneans of the genus Dactylogyrus Diesing, 1850, the largest genus in the family Dactylogyridae, mostly parasitize the gills of cyprinoid hosts; however, only 3 Dactylogyrus' mitochondrial genomes (mitogenomes) are studied so far. The aim of this research is to extend our understanding of the mitogenomes of Dactylogyrus. We sequenced the mitogenomes of D. crucifer and D. zandti isolated from Rutilus rutilus and Abramis brama orientalis in northwest China, and then we compared these mitogenomes with other monogeneans. We used Illumina NovaSeq to sequence the entire mitochondrial genomes of D. crucifer and D. zandti and characterized the mitogenomes to understand the gene structure, gene identity, the secondary structures of the 22 tRNA genes, and relative synonymous codon usage. We used the analytic Bayesian Information and Maximum Likelihood methods to determine their associated phylogenetic trees. The mitogenomes of D. crucifer and D. zandti were 14,403 and 18,584 bp, respectively. Organization and positioning of these genes were in accordance with Dactylogyrus lamellatus and Dactylogyrus tuba. The nucleotide composition of Dactylogyridae was different from other families of Monogenea, and the A+T count of genus Dactylogyrus (54 - 58.4 %) was lower than other genus species of the family Dactylogyridea (63.9 - 78.4 %) in protein-coding genes. Dactylogyrus members displayed a codon usage bias. The relative synonymous codon used by Dactylogyrus was not conserved and was lower than other monogeneans. The codon use patterns of closely-related species isolated from closely-related hosts were identical. Phylogenetic analyses using mitogenomic dataset produced Dactylogyrus isolated from host subfamily Leuciscinae formed a sister-group. Our results contributed significantly to an increased database of mitogenomes, more than 50 %, for Dactylogyrus that may help future studies of mitochondrial genes and codon uses for the analysis of monogenean phylogenetics.

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Macropsini is a tribe of Eurymelinae in the family Cicadellidae that is widely distributed worldwide. Still, its taxonomic status has been unstable, and the classification of certain clades at the genus level has been controversial. The aim of this study is to address the patterns and processes that explain the structure and the evolution of the mitogenomes of Macropsini, while contributing to the resolution of systematic issues involving five of their genera. To this task, the mitogenomes of 26 species of the tribe were sequenced and characterized, and their phylogenetic relationships were reconstructed. The results revealed that the nucleotide composition of mitochondrial genes in these 26 species was significantly skewed toward A and T. Codons ending with T or A in relative synonymous codon usage were significantly more prevalent than those ending with C or G. The parity plot, neutrality plot, and correspondence analysis revealed that mutation and selective pressure affect codon usage patterns. In the phylogenetic relationships of the Macropsini, the monophyly of Pedionis and Macropsis was well-supported. Meanwhile, Oncopsis revealed paraphyletic regarding Pediopsoides. In conclusion, this research not only contributes the valuable data to the understanding of the mitogenome of the Macropsini but also provides a reference for future investigations on codon usage patterns, potential adaptive evolution, and the phylogeny of the mitogenome within the subfamily Eurymelinae.

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Inflammatory bowel disease (IBD) is an inflammatory disorder of the gastrointestinal tract. The present study attempted to understand the codon usage preferences in genes associated with IBD progression. Compositional analysis, codon usage bias (CUB), Relative synonymous codon usage (RSCU), RNA structure, and expression analysis were performed to obtain a comprehensive picture of codon usage in IBD genes. Compositional analysis of 62 IBD-associated genes revealed that G and T are the most and least abundant nucleotides, respectively. ApG, CpA, and TpG dinucleotides were overrepresented or randomly used, while ApC, CpG, GpT, and TpA dinucleotides were either underrepresented or randomly used in genes related to IBD. The codons influencing the codon usage the most in IBD genes were CGC and AGG. A comparison of codon usage between IBD, and pancreatitis (non-IBD inflammatory disease) indicated that only codon CTG codon usage was significantly different between IBD and pancreatitis. At the same time, there were codons ATA, ACA, CGT, CAA, GTA, CCT, ATT, GCT, CGG, TTG, and CAG for whom codon usage was significantly different for IBD and housekeeping gene sets. The results suggest similar codon usage in at least two inflammatory disorders, IBD and pancreatitis. The analysis helps understand the codon biology, factors affecting gene expression of IBD-associated genes, and the evolution of these genes. The study helps reveal the molecular patterns associated with IBD.

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Malus baccata, a valuable germplasm resource in the genus Malus, is indigenous to China and widely distributed. However, little is known about the lineage composition and genetic basis of 'ZA', a mutant type of M. baccata. In this study, we compared the differences between 'ZA' and wild type from the perspective of morphology and ultrastructure and analyzed their chloroplast pigment content based on biochemical methods. Further, the complete mitogenome of M. baccata 'ZA' was assembled and obtained by next-generation sequencing. Subsequently, its molecular characteristics were analyzed using Geneious, MISA-web, and CodonW toolkits. Furthermore, by examining 106 Malus germplasms and 42 Rosaceae species, we deduced and elucidated the evolutionary position of M. baccata 'ZA', as well as interspecific variations among different individuals. In comparison, the total length of the 'ZA' mitogenome (GC content: 45.4%) is 374,023 bp, which is approximately 2.33 times larger than the size (160,202 bp) of the plastome (GC: 36.5%). The collinear analysis results revealed abundant repeats and genome rearrangements occurring between different Malus species. Additionally, we identified 14 plastid-driven fragment transfer events. A total of 54 genes have been annotated in the 'ZA' mitogenome, including 35 protein-coding genes, 16 tRNAs, and three rRNAs. By calculating nucleotide polymorphisms and selection pressure for 24 shared core mitochondrial CDSs from 42 Rosaceae species (including 'ZA'), we observed that the nad3 gene exhibited minimal variation, while nad4L appeared to be evolving rapidly. Population genetics analysis detected a total of 1578 high-quality variants (1424 SNPs, 60 insertions, and 94 deletions; variation rate: 1/237) among samples from 106 Malus individuals. Furthermore, by constructing phylogenetic trees based on both Malus and Rosaceae taxa datasets, it was preliminarily demonstrated that 'ZA' is closely related to M. baccata, M. sieversii, and other proximate species in terms of evolution. The sequencing data obtained in this study, along with our findings, contribute to expanding the mitogenomic resources available for Rosaceae research. They also hold reference significance for molecular identification studies as well as conservation and breeding efforts focused on excellent germplasms.

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The availability of high-throughput sequencing technologies increased our understanding of different genomes. However, the genomes of all living organisms still have many unidentified coding sequences. The increased number of missing small open reading frames (sORFs) is due to the length threshold used in most gene identification tools, which is true in the genic and, more importantly and surprisingly, in the intergenic regions. Scanning the cucumber genome intergenic regions revealed 420 723 sORF. We excluded 3850 sORF with similarities to annotated cucumber proteins. To propose the functionality of the remaining 416 873 sORF, we calculated their codon adaptation index (CAI). We found 398 937 novel sORF (nsORF) with CAI ≥ 0.7 that were further used for downstream analysis. Searching against the Rfam database revealed 109 nsORFs similar to multiple RNA families. Using SignalP-5.0 and NLS, identified 11 592 signal peptides. Five predicted proteins interacting with Meloidogyne incognita and Powdery mildew proteins were selected using published transcriptome data of host-pathogen interactions. Gene ontology enrichment interpreted the function of those proteins, illustrating that nsORFs' expression could contribute to the cucumber's response to biotic and abiotic stresses. This research highlights the importance of previously overlooked nsORFs in the cucumber genome and provides novel insights into their potential functions.

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Since 1996, circular codes in genes have been identified thanks to the development of 6 statistical approaches: trinucleotide frequencies per frame (Arquès and Michel, 1996), correlation functions per frame (Arquès and Michel, 1997), frame permuted trinucleotide frequencies (Frey and Michel, 2003, 2006), advanced statistical functions at the gene population level (Michel, 2015) and at the gene level (Michel, 2017). All these 3-frame statistical methods analyse the trinucleotide information in the 3 frames of genes: the reading frame and the 2 shifted frames. Notably, codon usage does not allow for the identification of circular codes (Michel, 2020). This has been a long-standing problem since 1996, hindering biologists' access to circular code theory. By considering circular code conditions resulting from code theory, particularly the concept of permutation class, and building upon previous statistical work, a new statistical approach based solely on the codon usage, i.e. a 1-frame statistical method, surprisingly reveals the maximal C3 self-complementary trinucleotide circular code X in bacterial genes and in average (bacterial, archaeal, eukaryotic) genes, and almost in archaeal genes. Additionally, a new parameter definition indicates that bacterial and archaeal genes exhibit codon usage dispersion of the same order of magnitude, but significantly higher than that observed in eukaryotic genes. This statistical finding may explain the greater variability of codes in eukaryotic genes compared to bacterial and archaeal genes, an issue that has been open for many years. Finally, biologists can now search for new (variant) circular codes at both the genome level (across all genes in a given genome) and the gene level using only codon usage, without the need for analysing the shifted frames.

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Oral squamous cell carcinoma (OSCC) is primarily known as oral cancer (OC) that mostly occurs in mouth, lips and tongue. Mutations in some of the genes cause OC and some genes are risk factors for progression of OC. In this study, we analyzed the compositional features and pattern of codon usage in genes involved in OC using computational method as no work was reported yet. Compositional features suggested that the overall GC content was higher i.e. genes were GC rich. Effective number of codons (ENC) values ranged from 34.6 to 55.9 with a mean value of 49.03±4.22 representing low codon usage bias (CUB). Correspondence analysis (COA) suggested that the codon usage pattern was different in different genes. In genes associated with OC, highly significant correlation was observed between GC12 and GC3 (r=0.454, p<0.01) suggesting that directional mutation affected all the three codon positions. This is the first report on pattern of codon usage pattern on genes involved in OC, which not only alludes a new perspective for elucidating the mechanisms of biased usage of synonymous codons but also provide valuable clues for molecular genetic engineering.

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Despite the highly conserved nature of the genetic code, the frequency of usage of each codon can vary significantly. The evolution of codon usage is shaped by two main evolutionary forces: mutational bias and selection pressures. These pressures can be driven by environmental factors, but also by the need for efficient translation, which depends heavily on the concentration of transfer RNAs (tRNAs) within the cell. The data presented here supports the proposal that tRNA modifications play a key role in shaping the overall preference of codon usage in proteobacteria. Interestingly, some codons, such as CGA and AGG (encoding arginine), exhibit a surprisingly low level of variation in their frequency of usage, even across genomes with differing GC content. These findings suggest that the evolution of GC content in proteobacterial genomes might be primarily driven by changes in the usage of a specific subset of codons, whose usage is itself influenced by tRNA modifications.

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Peste des petits ruminants virus (PPRV) is an infectious pathogen; causing highly contagious, acute febrile, and economically important disease of small ruminants. The virus is known to have intrinsic ability to adapt new hosts and to cross the species barrier. The incidence of PPR has already been reported in unusual host species such as camels, bovines, and wild animals from spill-over or natural infection. Still, there are elementary gaps in our knowledge of the extent of susceptibility of camel to PPRV and the adaptability of PPRV to camel. The present study delineates the potential role of preferential codon usage patterns responsible for adaptation, host immune evasion, and transmission of PPRV to unusual hosts like old world camel species namely, dromedary and bactrian camel. The results indicate codon usage of the PPRV genome is functioned by an interplay of mutational pressure and natural selection to exhort the adaptation and fitness of PPRV in probable hosts. The indices of natural selection like the relative codon deoptimization index (RCDI) and codon adaptation index (CAI) predict the ability of PPRV to adapt and evolve in camel species. The analysis also depicts the potential role of the CpG depletion mechanism employed by PPRV to evade host adaptive immune response. The report emphasizes the need for a comprehensive national PPR surveillance plan in unusual hosts like camels for the successful implementation of the PPR Global Eradication Programme (PPR- GEP).

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Ranaviruses, members of the genus Ranavirus within the family Iridoviridae, have become a significant concern for amphibian populations globally, along with other cold-blooded vertebrates, due to their emergence as a significant threat. We employed bioinformatics tools to examine the codon usage patterns in 61 DNA pol genes from Ranavirus, Lymphocystivirus, Megalocytivirus, and two unclassified ranaviruses, as no prior studies had been conducted on this topic. The results showed a slight or low level of codon usage bias (CUB) in the DNA pol genes of Ranavirus. Relative synonymous codon usage (RSCU) analysis indicated that the predominant codons favored in Ranavirus DNA pol genes terminate with C or G. Correlation analysis examining nucleotide content, third codon position, effective number of codons (ENC), correspondence analysis (COA), Aroma values, and GRAVY values indicated that the CUB across DNA pol genes could be influenced by both mutation pressure and natural selection. The neutrality plot indicated that natural selection is the primary factor driving codon usage. Furthermore, the analysis of the codon adaptation index (CAI) illustrated the robust adaptability of Ranavirus DNA pol genes to their hosts. Analysis of the relative codon deoptimization index (RCDI) suggested that Ranavirus DNA pol genes underwent greater selection pressure from their hosts. These findings will aid in comprehending the factors influencing the evolution and adaptation of Ranavirus to its hosts.

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The codon usage bias (CUB) of genes encoded by different species' genomes varies greatly. The analysis of codon usage patterns enriches our comprehension of genetic and evolutionary characteristics across diverse species. In this study, we performed a genome-wide analysis of CUB and its influencing factors in six sequenced Eimeria species that cause coccidiosis in poultry: Eimeria acervulina, Eimeria necatrix, Eimeria brunetti, Eimeria tenella, Eimeria praecox, and Eimeria maxima. The GC content of protein-coding genes varies between 52.67% and 58.24% among the six Eimeria species. The distribution trend of GC content at different codon positions follows GC1 > GC3 > GC2. Most high-frequency codons tend to end with C/G, except in E. maxima. Additionally, there is a positive correlation between GC3 content and GC3s/C3s, but a significantly negative correlation with A3s. Analysis of the ENC-Plot, neutrality plot, and PR2-bias plot suggests that selection pressure has a stronger influence than mutational pressure on CUB in the six Eimeria genomes. Finally, we identified from 11 to 15 optimal codons, with GCA, CAG, and AGC being the most commonly used optimal codons across these species. This study offers a thorough exploration of the relationships between CUB and selection pressures within the protein-coding genes of Eimeria species. Genetic evolution in these species appears to be influenced by mutations and selection pressures. Additionally, the findings shed light on unique characteristics and evolutionary traits specific to the six Eimeria species.

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Ergosterols are essential components of fungal plasma membranes. Inhibitors targeting ergosterol biosynthesis (ERG) genes are critical for controlling fungal pathogens, including Magnaporthe oryzae, the fungus that causes rice blast. However, the translational mechanisms governing ERG gene expression remain largely unexplored. Here, we show that the Trm6/Trm61 complex catalyzes dynamic N1-methyladenosine at position 58 (m1A58) in 51 transfer RNAs (tRNAs) of M. oryzae, significantly influencing translation at both the initiation and elongation stages. Notably, tRNA m1A58 promotes elongation speed at most cognate codons mainly by enhancing eEF1-tRNA binding rather than affecting tRNA abundance or charging. The absence of m1A58 leads to substantial decreases in the translation of ERG genes, ergosterol production, and, consequently, fungal virulence. Simultaneously targeting the Trm6/Trm61 complex and the ergosterol biosynthesis pathway markedly improves rice blast control. Our findings demonstrate an important role of m1A58-mediated translational regulation in ergosterol production and fungal infection, offering a potential strategy for fungicide development.

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Codon usage bias, or the unequal use of synonymous codons, is observed across genes, genomes, and between species. It has been implicated in many cellular functions, such as translation dynamics and transcript stability, but can also be shaped by neutral forces. We characterized codon usage across 1,154 strains from 1,051 species from the fungal subphylum Saccharomycotina to gain insight into the biases, molecular mechanisms, evolution, and genomic features contributing to codon usage patterns. We found a general preference for A/T-ending codons and correlations between codon usage bias, GC content, and tRNA-ome size. Codon usage bias is distinct between the 12 orders to such a degree that yeasts can be classified with an accuracy greater than 90% using a machine-learning algorithm. We also characterized the degree to which codon usage bias is impacted by translational selection. We found it was influenced by a combination of features, including the number of coding sequences, BUSCO count, and genome length. Our analysis also revealed an extreme bias in codon usage in the Saccharomycodales associated with a lack of predicted arginine tRNAs that decode CGN codons, leaving only the AGN codons to encode arginine. Analysis of Saccharomycodales gene expression, tRNA sequences, and codon evolution suggests that avoidance of the CGN codons is associated with a decline in arginine tRNA function. Consistent with previous findings, codon usage bias within the Saccharomycotina is shaped by genomic features and GC bias. However, we find cases of extreme codon usage preference and avoidance along yeast lineages, suggesting additional forces may be shaping the evolution of specific codons.