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PubMed2025

Codon usage of human DNA viruses and its similarity to certain host genes.

Codon usages of DNA viruses had previously been shown to associate with their genome size. Codon usage of various human DNA viruses was compared to those of human genes to further understand viral codon usage and its roles in viral-host interaction. Codon usage bias in both large and small genome human DNA viruses was dominantly driven by translation selection. Non-optimal codon usage in small DNA viruses showed similarity to cell cycle-related genes, whereas codon usage of large DNA viruses was more diverse, herpesviruses showed more heterogeneity than human adenoviruses, while poxviruses showed a clear bimodal pattern. Some of the large DNA viruses such as herpes simplex and molluscum contagiosum viruses showed more optimal codon usage. Enrichment analysis identified some groups of human genes with similar codon usage to each group of these viruses. These host genes with similarity in codon usages to those of viruses may be efficiently expressed in infected cells and involved in their life cycle, pathogenesis and/or immune evasion.

Humans↗

PubMed2026

Mitochondrial genomes of Dactylogyrus wunderi (Monopisthocotyla: Dactylogyridae): structural features, codon usage patterns, and phylogenetic implications.

BACKGROUND: Codon usage bias (CUB) is a common phenomenon reported among many species and genes, but its unique characteristics in the mitochondrial genome of class Monopisthocotyla remain unknown. METHODS: The complete mitochondrial genome of Dactylogyrus wunderi was sequenced and characterized, and the mitochondrial genome compositions and CUB of six Dactylogyrus species and 35 Monopisthocotyla species were analyzed using bioinformatics methods. RESULTS: The mitochondrial genome of D. wunderi is a typical circular structure in length of 14,920 bp. The A + T contents of the six Dactylogyrus species (58.4% ± 5.7%) were significantly lower than that of Monopisthocotyla species (71.0% ± 5.80%, p < 0.01). Neutrality plot analysis showed slopes of 0.3136 and 0.389 in the six Dactylogyrus and the 35 Monopisthocotyla species, respectively. Furthermore, 98.3% and 77.4% of the genes in the six Dactylogyrus and the Monopisthocotyla species, respectively, had effective number of codons (ENC) higher than 35, but 23.3% and 0.5% genes of ENC ratio ranged from - 0.05 to 0.05 in the six Dactylogyrus and Monopisthocotyla species. Phylogenetic analysis revealed that, within the context of the sampled taxa, the families of Monopisthocotyla were monophyletic groups, except for Ancyrocephalidae. CONCLUSIONS: The nucleotide composition had AT base bias in Monopisthocotyla, and natural selection was the main factor affecting CUB in the mitochondrial genomes of Monopisthocotyla species. These results provided insights into the factors affecting CUB in Monopisthocotyla species and deepened our insight of phylogeny, evolution, and codon usage of Monopisthocotyla.

Genome, Mitochondrial↗

PubMed2026

Natural Selection Drives Codon Usage Bias in the Mitochondrial Genome of Ligula intestinalis (Linnaeus, 1758) Gmelin, 1790 (Cestoda: Diphyllobothriidea): Insights from Comparative Genomics and Optimal Codon Identification.

Codon usage bias (CUB) is a useful indicator of evolutionary forces shaping mitochondrial genomes. Codon usage bias in mitochondrial genomes of Diphyllobothriidae and especially in Ligula intestinalis was characterized. The roles of natural selection and mutation pressure in framing this bias were evaluated on the basis of 12 protein-coding genes in Diphyllobothriidae. The complete mitogenome (13,725 bp) of L. intestinalis comprises 12 protein-coding genes (PCGs), 22 tRNAs, and two rRNAs, all positioned on the heavy strand, and contains an overall AT content of 66.15%. The mean CAI (0.176), CBI (-0.105), and ENC (45.33) and an evident preference for U-ending codons observed in all examined genes indicate weak CUB. Neutrality, ENC, and PR2 plots consistently demonstrate that natural selection is the predominant force driving CUB and contributes approximately 56% in L. intestinalis and 83% in other Diphyllobothriidea species, with mutation pressure playing a secondary role. Phylogenetic reconstruction supported the monophyly of Diphyllobothriidea, confirmed the paraphyly of Diphyllobothrium as traditionally defined, and placed Ligula and Digramma as sister taxa. These findings clarify the evolutionary constraints governing codon usage in cestode mitogenomes and provide practical resources for codon optimization in heterologous gene expression and genetic studies of this economically important parasite.

Diphyllobothriidea↗

PubMed2026

Comprehensive analysis of synonymous codon usage bias and evolutionary dynamics in the chloroplast genomes of eight Coptis species.

Coptis is a medically important genus renowned for producing valuable isoquinoline alkaloids. Although its chloroplast genomes encode key components for photosynthesis and plastid gene expression, the evolutionary constraints acting on their coding sequences and synonymous codon usage remain poorly resolved. Here, we combined a transparent taxon-level sampling strategy with comparative analyses of chloroplast CDSs from eight Coptis taxa. We quantified nucleotide composition, relative synonymous codon usage, effective number of codons, neutrality and PR2 patterns, and correspondence analysis, and then integrated these results with a core-CDS distance analysis and gene-wise pairwise dN/dS estimates. The chloroplast genomes showed a conserved AT-rich composition, especially at the third codon position (GC3 approximately 30.3-30.8%), with a consistent GC1 > GC2 > GC3 trend. Thirty preferred codons were detected, 28 ending in A/T, and eleven optimal codons were shared across the genus. The core-CDS distance analysis recovered a close relationship between C. chinensis and C. chinensis var. brevisepala, whereas most coding genes showed dN/dS values below one, consistent with pervasive purifying constraint. Across 48 consistently filtered CDSs, GC3s was negatively associated with mean dN (Spearman rho = -0.404, P = 0.00439) and CAI was positively associated with mean dN (rho = 0.303, P = 0.0361), whereas the remaining associations were not significant (all P > = 0.0972). These results extend codon-usage analysis by linking synonymous-site composition to coding-sequence evolution within Coptis, while providing a hypothesis-generating resource for future plastid engineering studies.

Genome, Chloroplast↗

PubMed2025

Translation of the downstream ORF from bicistronic mRNAs by human cells: Impact of codon usage and splicing in the upstream ORF.

Biochemistry textbooks describe eukaryotic mRNAs as monocistronic. However, increasing evidence reveals the widespread presence and translation of upstream open reading frames preceding the "main" ORF. DNA and RNA viruses infecting eukaryotes often produce polycistronic mRNAs and viruses have evolved multiple ways of manipulating the host's translation machinery. Here, we introduce an experimental model to study gene expression regulation from virus-like bicistronic mRNAs in human cells. The model consists of a short upstream ORF and a reporter downstream ORF encoding a fluorescent protein. We have engineered synonymous variants of the upstream ORF to explore large parameter space, including codon usage preferences, mRNA folding features, and splicing propensity. We show that human translation machinery can translate the downstream ORF from bicistronic mRNAs, albeit reporter protein levels are thousand times lower than those from the upstream ORF. Furthermore, synonymous recoding of the upstream ORF exclusively during elongation significantly influences its own translation efficiency, reveals cryptic splice signals, and modulates the probability of downstream ORF translation. Our results are consistent with a leaky scanning mechanism facilitating downstream ORF translation from bicistronic mRNAs in human cells, offering new insights into the role of upstream ORFs in translation regulation.

Humans↗

PubMed2025

Unconventional codon usage bias mediates mRNA translational dynamics in macrophages.

Macrophages require rapid and tightly controlled regulatory mechanisms to respond to environmental disruptions. While transcriptional regulation has been well characterized, the mechanisms underlying translational control in macrophages remain poorly understood. Here, we investigated the dynamics of mRNA translation in mouse macrophages during acute, intermediate, and prolonged LPS exposure. Our results reveal clear phase-specific translational regulation during macrophage polarization, which initially increases the synthesis of inflammatory mediators and cytokines, while simultaneously suppressing the expression of cell cycle-related genes. Mechanistically, we observed pervasive upstream translation in the 5' UTRs of cell cycle-related mRNAs, which contributes to cell cycle arrest during the early phase of inflammatory response. Notably, we identified a unique codon preference toward A/U in the third position of codons in macrophages, which contrasts with the G/C preference commonly observed in other tissues. AU codon preference increases the stability and translation efficiency of cell cycle-related mRNAs, promoting cell cycle restoration after extended LPS exposure. These findings reveal that uORF translation and codon usage bias are critical components of translational regulation during macrophage polarization, highlighting a potential therapeutic intervention for modulating immune activation via macrophage-specific codon optimization.

Animals↗

PubMed2026

Insights Into the Structural Features, Codon Usage Patterns, and Phylogenetic Analysis in Neoniphon argenteus (Teleostei: Holocentriformes) Based on Complete Mitochondrial Genome.

Neoniphon argenteus, a widely distributed nocturnal coral reef fish in the family Holocentridae, plays an important role in maintaining coral reef ecosystem health, yet its phylogenetic position remains poorly resolved. To bridge this gap, we sequenced and analyzed the complete mitochondrial genome of a specimen from the South China Sea to characterize its structural features, codon usage patterns, and phylogenetic relationships. The 16,569 bp mitogenome (GenBank: PP190474.1) encodes 13 protein-coding genes (PCGs), 22 tRNAs, two rRNAs, and two non-coding regions, exhibiting a distinct A + T bias. All tRNAs fold into typical cloverleaf secondary structures except tRNA-Ser (AGN), which lacks the dihydrouridine (DHU) arm. The control region contains palindromic motifs (TACAT/ATGTA) capable of forming hairpin structures and five conserved sequence blocks, whereas the OL region harbors a conserved 5'-GCCGG-3' motif. RSCU analysis revealed 31 frequently used codons (RSCU > 1) with a pronounced preference for A/C-ending codons. The ΔRSCU method identified 10 candidate optimal codons (GCA, CAA, GAA, GGA, AUU, CUA, CCA, CGA, ACA, and GUC). Selection pressure analysis using EasyCodeML and site-specific models indicated that all PCGs are predominantly under purifying selection, with no significant evidence of pervasive positive selection. ND6 exhibited elevated pairwise Ka/Ks ratios (mean = 1.209 ± 0.047), consistent with reduced selective constraint rather than adaptive evolution. Phylogenetic analysis of 19 Holocentriformes species using maximum likelihood and Bayesian inference with partitioned models based on 13 PCGs and two rRNA genes (12S and 16S) assigned all taxa to two well-supported subfamilies (Holocentrinae and Myripristinae). Within Holocentrinae, Neoniphon species form a monophyletic clade nested within a paraphyletic Sargocentron, suggesting that the genus Sargocentron as currently defined is not monophyletic. This study provides useful baseline molecular data for further exploration of the evolutionary history of N. argenteus and other members of Holocentriformes.

Holocentridae↗

PubMed1979

On codon usage.

Explore the source record for details and available documents.

Codon↗

PubMed1979

The preferential codon usages in variable and constant regions of immunoglobulin genes are quite distinct from each other.

The pattern of codon utilization in the variable and constant regions of immunoglobulin genes are compared. It is shown that, in these regions, codon utilizations are quite distinct from one another: For most degenerate codons, there is a selective bias that prefers C and/or G ending codons to U and/or A ending codons in the constant region compared with the bias in the variable region. This would strongly suggest that, in immunoglobulin genes, the bias in code word usage is determined by other factors than those concerning with the translational mechanism such as tRNA availability and codon-anticodon interaction. A possibility is also suggested that this differance of code word usage between them is due to the existence of secondary structure in the constant region but not in the variable region.

Anticodon↗

PubMed2026

De Novo Assembly and Comparative Analysis of the Complete Mitochondrial Genome of Mesenchytraeus (Annelida, Enchytraeidae).

The Changbai Mountain range is one of the key glacial refugia in Northeast Asia. Mesenchytraeus exhibits high species diversity, strong endemism, and widespread cryptic species in this region, for which mitogenomes provide useful molecular markers for exploring cryptic species complexes. This makes Mesenchytraeus an ideal model for studying mitogenome evolution among closely related lineages; however, no mitogenome data have been reported for this genus to date. In this study, we performed de novo assembly, annotation, and comparative analysis of the mitogenomes of 13 Mesenchytraeus species (14 individuals) from Changbai Mountain. All mitogenomes are typical circular molecules containing 37 genes, but putative control regions are rearranged and consistently located between ATP6 and trnR. All species exhibit annelid-specific strand nucleotide biases, characterized by negative GC skew and near-zero AT skew. Codon usage analysis reveals that codon families with wobble U are significantly biased toward mtDNA codons, whereas those with wobble C or G are biased toward non-mtDNA codons, suggesting a conserved mitochondrial codon usage pattern in annelids. All tRNAs form typical cloverleaf secondary structures except trnS2, which lacks the D-stem and the dihydrouridine (DHU) arm in some species. The putative control regions commonly contain complex palindromic repeats, hairpins, and repetitive elements, and may harbor dual replication origins. Phylogenetic analyses support the monophyly of Mesenchytraeus and reveal significant molecular divergence among morphologically cryptic species. This study provides the first mitogenome dataset for Mesenchytraeus and offers new insights into the evolution and replication mechanisms of mitogenomes in Clitellata and broader Annelida.

Mesenchytraeus↗

PubMed2026

Multilayered nucleotide organization reveals purifying selection and host-driven adaptation in CPV and FPV.

Since feline panleukopenia virus (FPV) is considered the most likely ancestor of canine parvovirus (CPV), comprehensive comparisons of nucleotide organization in corresponding viral genes between CPV and FPV may provide novel insights into the evolutionary dynamics underlying the divergence of these two viruses. Here, we characterize the evolutionary patterns of CPV and FPV genes across multiple levels of nucleotide organization. Both viruses exhibited highly conserved nucleotide usage at nonsynonymous sites, with Ka/Ks patterns consistent with strong purifying selection, whereas synonymous sites showed greater variability. CpG dinucleotides were markedly underrepresented across all four viral genes, suggesting host-associated selective pressure and/or intrinsic nucleotide compositional constraints. Extensive nonrandom biases in synonymous codon usage, codon neighboring nucleotide context, and codon pair usage further revealed fine-scale genomic optimization shaped by natural selection and nucleotide compositional constraints. Structural protein genes (VP1 and VP2) displayed stronger codon usage bias and higher tRNA adaptation than nonstructural genes. Moreover, CPV genes showed greater translational adaptation to feline hosts than to canine hosts. These findings highlight how closely related parvoviruses exploit flexible nucleotide organization to facilitate host adaptation while maintaining essential protein functions.

Animals↗

PubMed2025

Horizontal transfer of accessory chromosomes in fungi - a regulated process for exchange of genetic material?

Horizontal transfer of entire chromosomes has been reported in several fungal pathogens, often significantly impacting the fitness of the recipient fungus. All documented instances of horizontal chromosome transfers (HCTs) showed a marked propensity for accessory chromosomes, consistently involving the transfer of an accessory chromosome while other chromosomes were seldom, if ever, co-transferred. The mechanisms underlying HCTs, as well as the factors regulating the specificity of HCTs for accessory chromosomes, remain unclear. In this perspective, we provide an overview of the observed propensity in reported cases of horizontal chromosome transfers. We hypothesize the existence of a signal that distinguishes mobile, i.e., horizontally transferred, accessory chromosomes from the rest of the donor genome. Recent findings in Metarhizium robertsii and Magnaporthe oryzae, suggest that a mobile accessory chromosome may contain putative histones and/or histone modifiers, which could generate such a signal. Based on this, we propose that mobile accessory chromosomes may encode the machinery required for their own horizontal transmission, implying that HCT could be a regulated process. Finally, we present evidence of substantial differences in codon usage bias between core and accessory chromosomes in 14 out of 19 analysed fungal species and strains. Such differences in codon usage bias could indicate past horizontal transfers of these accessory chromosomes. Interestingly, HCT was previously unknown for many of these species, suggesting that the horizontal transfer of accessory chromosomes may be more widespread than previously thought, and therefore an important factor in fungal genome evolution.

Gene Transfer, Horizontal↗

PubMed2026

Molecular Evolution and Expression Analysis of the ADH Gene Family in Apple Bud Mutants.

Alcohol dehydrogenase (ADH) catalyzes the reduction of aldehydes to alcohols, key precursor substrates for volatile ester biosynthesis, which determines the characteristic aroma of apple fruit. However, a comprehensive genome-wide investigation of the ADH gene family in apple has been lacking. In this study, we systematically identified ADH genes in the apple genome using integrated bioinformatics approaches, including phylogenetic analysis, synteny evaluation, promoter cis-element prediction, codon usage bias assessment, and protein interaction network modeling. Expression patterns were examined through transcriptomic data and validated by RT-qPCR analysis across different organs and among 'Red Delicious' and its four bud mutant lines. We identified 44 ADH genes, with 12 forming a prominent cluster on chromosome 1. RT-qPCR analysis revealed that MdADH20 was dramatically upregulated in the 'Red Chief' mutant (relative expression of 59.38), suggesting its pivotal role. Phylogenetic analysis revealed a close evolutionary relationship with wild strawberry. The encoded proteins were generally stable and predominantly localized to the cytoplasm. Promoter analysis showed enrichment of growth/development-related and ARE elements, while codon usage analysis identified AGA, GCU, GUU, and CUU as preferred codons. Protein interaction prediction suggested MdADH19 and MdADH20 as hub proteins. Expression profiling and RT-qPCR further identified MdADH20 as a core candidate gene, characterized by its stable and high expression, particularly in the 'Red Delicious' mutant. Its central position in the predicted protein-protein interaction network suggests a potential regulatory role in the aroma biosynthesis pathway of apple fruit. This study provides the first systematic genome-wide characterization of the apple ADH gene family, establishing a theoretical groundwork for deciphering aroma biosynthesis mechanisms and offering potential target genes for flavor improvement through bud mutation breeding strategies.

ADH gene family↗

PubMed2026

Dietary arginine drives codon-dependent MHC class I translation and improves immunity in colon tumorigenesis and respiratory viral infection.

Amino acid levels fluctuate across diverse pathological conditions. Whether such amino acid modulations directly shape pathophysiology by regulating host gene expression remains unknown. We found that extracellular arginine restriction, observed in cancer and infection, represses specific arginine tRNAs-directly suppressing translation of major histocompatibility complex I (MHC class I) and antigen presentation. Arginine regulation of MHC class I was codon-usage dependent, as synonymous codon mutations prevented MHC class I modulation. Dietary arginine restriction impaired anti-viral immunity against influenza and SARS-CoV-2 and increased colon tumorigenesis. Conversely, increasing arginine availability via dietary supplementation or myeloid-specific arginase 1 deletion enhanced MHC class I protein levels, suppressed colon tumorigenesis, and improved viral infection outcomes. These disease-modulating effects were abolished in β2-microglobulin (B2m)-deficient mice. Thus, dietary modulation of a single amino acid critically influences codon-biased translation and MHC class I-mediated immunity to respiratory viral infections and cancer, revealing an unexpected mechanism and disease hazard for arginine deficiency and highlighting potential for amino acid-based translation modulation therapy.

Animals↗

PubMed2026

Codon bias variation in Staphylococcus aureus.

BACKGROUND: Staphylococcus aureus causes a multiplicity of human diseases acquired in community and healthcare settings alike around the globe. While most studies focus on coding changes to assess genome evolution and study genetic adaptation, interrogation of silent mutations in the form of synonymous codon usage bias is less well-studied. As such, understanding of patterns in codon bias at the gene and genome levels, and how codon bias impacts protein expression in S. aureus remains incomplete. METHODS: The codon bias of 2,565 protein encoding genes from NCTC 8325 was queried against all publicly available closed S. aureus genomes. Using public BioSample data, genomes were sorted by disease state, submitting institution, and collection site. Codon bias was assessed at the level of gene and genome using the codon adaptation index (CAI), calculated using 30S and 50S ribosomal genes. Gene set enrichment analysis was applied to determine associations between physiological functions, CAI gene scores, and interquartile ranges. CAI scores were also compared to an in vitro S. aureus proteomics database to correlate codon bias and protein expression. RESULTS: CAI scores varied within and between isolates at the gene and genome levels. Genes with ribosome-associated functions were most enriched among high CAI genes, and had low CAI interquartile ranges (IQR), suggesting selective pressure to maintain high expression of these genes across all S. aureus isolates. Genome sequences submitted by Aga Khan University Hospital, Nairobi, Kenya were most different from others. For the LAC USA 300 strain, CAI and protein expression were moderately positively correlated (cor = 0.534, p < 2.2e-16). CONCLUSIONS: Codon bias in S. aureus was shown to vary between gene, and to be a source of genetic variation between isolates; CAI and in vitro protein expression were positively correlated.

Staphylococcus aureus↗

PubMed2025

Automated Machine Learning Tools to Build Regression Models for Schizosaccharomyces pombe Omics Data.

Machine learning is a powerful tool for analyzing biological data and making useful predictions. The surge of biological data from high-throughput omics technologies has raised the need for modeling approaches capable of tackling such amounts of data, which is pivotal to understanding the nature of complex molecular systems. Here, we show how to construct a simple model using automated machine learning (AutoML) to predict protein abundance in Schizosaccharomyces pombe, using data obtained from codon usage bias and quantitative proteomics.

Machine Learning↗

PubMed2026

Hurdles to horizontal gene transfer: species-specific effects of synonymous variation and plasmid copy number determine antibiotic resistance phenotype.

Could codon composition condition the immediate success and the orientation of horizontal gene transfer? Horizontal gene transfer represents a change in the genome of expression of the transferred gene, and experimental evidence has accumulated indicating that the codon composition of a sequence is an important determinant of its compatibility with the translation machinery of the genome in which it is expressed. This suggests that codon composition influences the phenotype and the fitness conferred by a transferred gene and thus the immediate success of the transfer. To directly test this hypothesis, we characterized the resistance conferred by synonymous variants of a gentamicin resistance gene in three bacterial species: Escherichia coli, Acinetobacter baylyi and Pseudomonas aeruginosa. The strongest determinant of the resistance level conferred was the species in which the resistance gene was transferred, very likely because of important differences in the copy number of the plasmid carrying the gene. Significant differences in resistance were also found between synonymous variants within each of the three species, but more importantly, there was a strong interaction between species and variant: variants conferring high resistance in one species confer low resistance in another. However, the similarity in codon usage between the synonymous variants and the host genome only explained part of the phenotypic differences between variants in one species, P. aeruginosa. Further investigation of alternative explanations did not reveal common universal mechanisms across our three bacterial species. We conclude that codon composition can be a determinant of post-horizontal gene transfer success. However, there are multiple paths leading from synonymous sequence to phenotype, and sensitivity to these different paths is species-specific.

Gene Transfer, Horizontal↗

PubMed2026

The large mitochondrial genome of Syndiclis anlungensis (Lauraceae): Genome structure, comparative analysis, and phylogenetic relationships among Syndiclis species.

The complete mitochondrial genome (mitogenome) of Syndiclis anlungensis, a critically endangered tropical tree, was determined in this study. The mitogenome spans 2,368,454 bp across four contigs and harbors 41 protein-coding genes, 22 tRNA genes, and three rRNA genes. Potential mutation regions, including 1317 repeat sequences and 698 simple sequence repeats (SSRs), were accurately located in the S. anlungensis mitogenome. Sixty-five transferred fragments of the repeats were found between its mitochondrial and chloroplast genomes. When compared to three other Laurales mitogenomes, extensive gene order shuffling is evident, leaving only five conserved gene clusters intact. Codon usage analysis reveals a pronounced A/T bias in both mitochondrial and chloroplast genes, and three mitochondrial genes (atp9, rps19, and sdh3) stand out for their high divergence across eleven Syndiclis taxa. Selection analyses indicate strong purifying pressure on rpl2, rpl16, and sdh3 (Ka/Ks < 1), with no positive selection detected. Using 41 mitochondrial protein-coding gene sequences from sixteen and three individuals of Syndiclis and Beilschmiedia species, respectively, our phylogenetic tree recovers Syndiclis as monophyletic, with two well-supported clades: one includes S. anlungensis, S. chinensis, S. lotungensis, S. marlipoensis, and a putative new Syndiclis species from Yunnan; the other contains S. furfuracea, S. hongkongensis, S. kwangsiensis, and three putative new Syndiclis species from Guangdong and Vietnam.

Genome, Mitochondrial↗