Codon Positions Research Articles

Differential Synonymous Codon Selection in the B56 Gene Family of PP2A Regulatory Subunits.

Protein phosphatase 2A (PP2A) functions as a tumor suppressor and consists of a scaffolding, catalytic, and regulatory subunit. The B56 gene family of regulatory subunits impart distinct functions onto PP2A. Codon usage bias (CUB) involves the selection of synonymous codons, which can affect gene expression by modulating processes such as transcription and translation. CUB can vary along the length of a gene, and differential use of synonymous codons can be important in the divergence of gene families. The N-termini of the gene product encoded by B56α possessed high CUB, high GC content at the third codon position (GC3), and high rare codon content. In addition, differential CUB was found in the sequence encoding two B56γ N-terminal splice forms. The sequence encoding the N-termini of B56γ/γ, relative to B56δ/γ, displayed CUB, utilized more frequent codons, and had higher GC3 content. B56α mRNA had stronger than predicted secondary structure at their 5' end, and the B56δ/γ splice variants had long regions of weaker than predicted secondary structure at their 5' end. The data suggest that B56α is expressed at relatively low levels as compared to the other B56 isoforms and that the B56δ/γ splice variant is expressed more highly than B56γ/γ.

Comparative and phylogenetic analysis of the complete chloroplast genomes of Uncaria (Rubiaceae) species.

The genus Uncaria is famous for its high medicinal value. However, the high morphological similarities and unclear interspecific genetic relationships have posed challenges to the classification and identification of Uncaria species. Here, we newly sequenced six chloroplast genomes of Uncaria species: U. hirsuta, U. rhynchophylla, U. rhynchophylloides, U. homomalla, U. sinensis, and U. lancifolia. Comparisons among the chloroplast genomes of Uncaria species showed their conservation in structure, gene content, and order. Ten highly variable loci could be potentially used as specific molecular markers in the identification of Uncaria species. The third position of codons tended to use A/U base, and natural selection contributed more to the formation of codon usage bias in comparison to mutation pressure. Four genes (rbcL, ndhF, rps8, and ycf2) were detected to be subjected to positive selection. Phylogenetic analysis showed that the genus Uncaria was a monophyletic group, belonging to the tribe Naucleeae. Moreover, U. sinensis was not a variant of U. rhynchophylla. U. rhynchophylloides and U. rhynchophylla were not the same species. The results of the comparative and phylogenetic analysis provide valuable references for further research studies of classification, identification, breeding improvement, and phylogenetic relationships in Uncaria species.

Chargaff's second parity rule lies at the origin of additive genetic interactions in quantitative traits to make omnigenic selection possible.

Francis Crick's central dogma provides a residue-by-residue mechanistic explanation of the flow of genetic information in living systems. However, this principle may not be sufficient for explaining how random mutations cause continuous variation of quantitative highly polygenic complex traits. Chargaff's second parity rule (CSPR), also referred to as intrastrand DNA symmetry, defined as near-exact equalities G ≈ C and A ≈ T within a single DNA strand, is a statistical property of cellular genomes. The phenomenon of intrastrand DNA symmetry was discovered more than 50 years ago; at present, it remains unclear what its biological role is, what the mechanisms are that force cellular genomes to comply strictly with CSPR, and why genomes of certain noncellular organisms have broken intrastrand DNA symmetry. The present work is aimed at studying a possible link between intrastrand DNA symmetry and the origin of genetic interactions in quantitative traits. Computational analysis of single-nucleotide polymorphisms in human and mouse populations and of nucleotide composition biases at different codon positions in bacterial and human proteomes. The analysis of mutation spectra inferred from single-nucleotide polymorphisms observed in murine and human populations revealed near-exact equalities of numbers of reverse complementary mutations, indicating that random genetic variations obey CSPR. Furthermore, nucleotide compositions of coding sequences proved to be statistically interwoven via CSPR because pyrimidine bias at the 3rd codon position compensates purine bias at the 1st and 2nd positions. According to Fisher's infinitesimal model, we propose that accumulation of reverse complementary mutations results in a continuous phenotypic variation due to small additive effects of statistically interwoven genetic variations. Therefore, additive genetic interactions can be inferred as a statistical entanglement of nucleotide compositions of separate genetic loci. CSPR challenges the neutral theory of molecular evolution-because all random mutations participate in variation of a trait-and provides an alternative solution to Haldane's dilemma by making a gene function diffuse. We propose that CSPR is symmetry of Fisher's infinitesimal model and that genetic information can be transferred in an implicit contactless manner.

Codon usage bias in the chloroplast genomes of Cymbidium species in Guizhou, China

Cymbidium plants play a vital role in biodiversity conservation, evolutionary research, and biological protection. Understanding codon usage bias (CUB) in Cymbidium plants is crucial for unraveling the mechanism of species evolution and gene expression. In this study, we systematically analyzed the CUB and identified sources of variance in chloroplast genomes of 12 Cymbidium species to explore the main factors influencing CUB. Using CodonW 1.4.2 software and CUSP program, we screened 52 coding DNA sequences (CDS) within the complete chloroplast genome sequences of the twelve Cymbidium species. Subsequently, neutral, ENC-plot, and PR2-plot mapping analyses were performed to explore the relationships between code usage and genetic elements. The results revealed a consistent bias for guanine-cytosine (GC) bases at the first and second positions (GC1 > GC2 > GC3) of chloroplast genome codons in all 12 Cymbidium species. Moreover, the third base of codons exhibited a predilection for adenine/thymine (A/T) or uracil (U). The effective number of codons (ENC) ranged from 48.6 % to 49.49 %, with an average of 49.07, indicating a weak CUB. Additionally, codon adaptation index (CAI) ranged from 0.167 to 0.171, further supporting the weak CUB. The mapping analyses consistently highlighted natural selection as the primary factor influencing CUB in the 12 orchid chloroplast genomes while acknowledging the impact of other factors, such as mutations. Through optical codon analysis, we identified the top ten preferred codons (UUA, AUU, UCU, CCU, ACU, GCU, AAA, CGA, AGU, and GGU), all of which ended with A or U. These findings provide valuable insights for future studies involving codon modification of foreign genes and the development of high-expression transgenic techniques in Cymbidium plants.

Environmental implications of codon usage bias in Crocus sativus and its impact on host pathogen interactions

Codon usage bias (CUB) is a ubiquitous phenomenon perseveres in genome of all the organisms. It impinges the gene expression and other genetic intricacies within a genome. The present study explains the pattern of codon usage in the protein coding sequence of Crocus sativus and its relation with gene expression. Gene expression analysis in C. sativus showed genes with high expression had a preference of G base at third position. CUB had an inverse relation with gene expression. Coding sequences with effective number of codons (ENC) < 50 had low Fragments Per Kilobase Million (FPKM) value while low codon bias group ENC >50 possessed high FPKM value. The low tAI values showed the low translation efficiency of genes in C. sativus. The non-significant MILC-based expression level predictor (MELP) and ENC correlation analysis suggested that expression of genes might not be associated with codon usage bias. ENC and PR-2 plot revealed mutation pressure and natural selection played role in shaping Codon usage patterns. However, neutrality plot conclusively depicted the dominance of natural selection in regulating the configuration of codons in all the selected species. In addition, the role of Codon usage bias regarding the predilection of fungal pathogens Aspergillus fumigatus, Fusarium oxysporum, Aspergillus niger and Aspergillus flavus towards host plant C. sativus has also been expounded. We found a similar trend of codon usage operative in plant and fungal pathogens as all the fungal pathogens and host plant showed similar GC rich genomic content as well as preference for GC ending codons at third codon position. This concurrence might be attributed for the colonization of fungal pathogens in C. sativus. Overall, different indices reflected a weak codon bias in the C. sativus, and its associated pathogens.

Human RSVA-ON1, The Only Genotype Present During 2019–2020 Winter Season in Riyadh, Saudi Arabia: A Retrospective Study

Aim: The study aimed to analyze human respiratory syncytial virus (hRSV) strains in nasopharyngeal aspirates obtained retrospectively. Materials &amp; methods: Clinical information of ARI patients (n = 53) was accessed and 2nd hypervariable region of G protein gene of RSV was sequenced and analyzed. Results: Cough (98.1%), fever 40 (75.4%) and shortness of breath 32 (60.3%) were the common symptom. Sequence determination (n = 45) categorized all the strains in ON1 genotype. Potential O- and N- glycosylation were observed at some sites and purifying selections were observed at 274 and 320 codon positions. Conclusion: The study reports replacement of other RSVA genotypes with ON1. The future course of studies should emphasize on clinical implications of presence of hRSVA-ON1 genotype in a given population.

Comparative analysis of codon usage patterns and phylogenetic implications of five mitochondrial genomes of the genus Japanagallia Ishihara, 1955 (Hemiptera, Cicadellidae, Megophthalminae).

Japanagallia is a genus of Cicadomorpha in the family of leafhoppers that are plant piercing-sucking insects, and it is difficult to distinguish by morphological characteristics. So far, only one complete mitochondrial genome data has been reported for the genus Japanagallia. Therefore, in order to better understand this group, we assembled and annotated the complete mitochondrial genomes of five Japanagallia species, and analyzed their codon usage patterns. Nucleotide composition analysis showed that AT content was higher than GC content, and the protein-coding sequences preferred to end with A/T at the third codon position. Relative synonymous codon usage analysis revealed most over-represented codon ends with A or T. Parity plot analysis revealed the codon usage bias of mitochondrial genes was influenced by both natural selection and mutation pressure. In the neutrality plot, the slopes of regression lines were < 0.5, suggesting that natural selection was playing a major role while mutation pressure was of minor importance. The effective number of codons showed that the codon usage bias between genes and genomes was low. Correspondence analysis revealed that the codon usage pattern differed among 13 protein-coding genes. Phylogenetic analyses based on three datasets using two methods (maximum likelihood and Bayesian inference), restored the Megophthalminae monophyly with high support values (bootstrap support values (BS) = 100, Bayesian posterior probability (PP) = 1). In the obtained topology, the seven Japanagallia species were clustered into a monophyletic group and formed a sister group with Durgade. In conclusion, our study can provide a reference for the future research on organism evolution, identification and phylogeny relationships of Japanagallia species.

Genomic epidemiology of SARS-CoV-2 from Uttar Pradesh, India

The various strains and mutations of SARS-CoV-2 have been tracked using several forms of genomic classification systems. The present study reports high-throughput sequencing and analysis of 99 SARS-CoV-2 specimens from Western Uttar Pradesh using sequences obtained from the GISAID database, followed by phylogeny and clade classification. Phylogenetic analysis revealed that Omicron lineages BA-2-like (55.55%) followed by Delta lineage-B.1.617.2 (45.5%) were predominantly circulating in this area Signature substitution at positions S: N501Y, S: D614G, S: T478K, S: K417N, S: E484A, S: P681H, and S: S477N were commonly detected in the Omicron variant-BA-2-like, however S: D614G, S: L452R, S: P681R and S: D950N were confined to Delta variant-B.1.617.2. We have also identified three escape variants in the S gene at codon position 19 (T19I/R), 484 (E484A/Q), and 681 (P681R/H) during the fourth and fifth waves in India. Based on the phylogenetic diversification studies and similar changes in other lineages, our analysis revealed indications of convergent evolution as the virus adjusts to the shifting immunological profile of its human host. To the best of our knowledge, this study is an approach to comprehensively map the circulating SARS-CoV-2 strains from Western Uttar Pradesh using an integrated approach of whole genome sequencing and phylogenetic analysis. These findings will be extremely valuable in developing a structured approach toward pandemic preparedness and evidence-based intervention plans in the future.

A full repertoire of Hemiptera genomes reveals a multi-step evolutionary trajectory of auto-RNA editing site in insect Adar gene

ABSTRACT Adenosine-to-inosine (A-to-I) RNA editing, mediated by metazoan ADAR enzymes, is a prevalent post-transcriptional modification that diversifies the proteome and promotes adaptive evolution of organisms. The Drosophila Adar gene has an auto-recoding site (termed S>G site) that forms a negative-feedback loop and stabilizes the global editing activity. However, the evolutionary trajectory of Adar S>G site in many other insects remains largely unknown, preventing us from a deeper understanding on the significance of this auto-editing mechanism. In this study, we retrieved the well-annotated genomes of 375 arthropod species including the five major insect orders (Lepidoptera, Diptera, Coleoptera, Hymenoptera and Hemiptera) and several outgroup species. We performed comparative genomic analysis on the Adar auto-recoding S>G site. We found that the ancestral state of insect S>G site was an uneditable serine codon (unSer) and that this state was largely maintained in Hymenoptera. The editable serine codon (edSer) appeared in the common ancestor of Lepidoptera, Diptera and Coleoptera and was almost fixed in the three orders. Interestingly, Hemiptera species possessed comparable numbers of unSer and edSer codons, and a few ‘intermediate codons’, demonstrating a multi-step evolutionary trace from unSer-to-edSer with non-synchronized mutations at three codon positions. We argue that the evolution of Adar S>G site is the best genomic evidence supporting the ‘proteomic diversifying hypothesis’ of RNA editing. Our work deepens our understanding on the evolutionary significance of Adar auto-recoding site which stabilizes the global editing activity and controls transcriptomic diversity.

Highly rearranged gene orders and rapid evolutionary rates in the mitochondrial genomes of Apodida (Echinodermata: Holothuroidea)

Mitochondrial genome (mitogenome) is a frequently-used tool for phylogenetic and evolutionary studies among metazoans, however, it was still poorly represented in some invertebrate groups, including holothurians. Apodida is one of the most ancient orders of Holothuroidea, with unique characteristics in lacking tube feet and the respiratory tree. Here, we sequenced six mitogenomes from the holothurian order Apodida (Synaptidae and Chiridotidae) and compared them with other available holothurian mitogenomes. The apodan mitogenomes present positive GC skews and negative AT skews, a pattern diametrically opposite to that found in the mitogenomes of other holothurians. The amino acid genetic distances of the 13 protein-coding genes (PCGs) were the highest between Apodida and other holothurians. The mitochondrial gene orders within Apodida were extensively rearranged at the species level, and also were unique from the arrangement patterns of other holothurians. Phylogenetic relationships based on two different criteria: (i) nucleotides sequences with all codon positions (PCG123) and (ii) Neutral Transitions Excluded model (NTE) confirmed the monophyly and basal position of the order Apodida with a long branch. The NTE phylogeny generated a low variation of branch length, but it did not ameliorate the long branch length of Apodida. The divergence time estimation suggested that the Apodida originated in the Middle Carboniferous, implying that they survived the extinction event that occurred in the boundary of the Permian and Triassic. The NTE dataset revealed younger age than that generated by PCG123 dataset. Apodida is accompanied by a faster evolutionary rate than other holothurians (0.0069 vs 0.0043 subs/s/my). The absence of tube feet and the respiratory tree may play an important role in the dramatic evolutionary changes of apodan mitogenomes.

An Evolutionary Perspective of Codon Usage Pattern, Dinucleotide Composition and Codon Pair Bias in Prunus Necrotic Ringspot Virus.

Prunus necrotic ringspot virus (PNRSV) is a significant virus of ornamental plants and fruit trees. It is essential to study this virus due to its impact on the horticultural industry. Several studies on PNRSV diversity and phytosanitary detection technology were reported, but the content on the codon usage bias (CUB), dinucleotide preference and codon pair bias (CPB) of PNRSV is still uncertain. We performed comprehensive analyses on a dataset consisting of 359 coat protein (CP) gene sequences in PNRSV to examine the characteristics of CUB, dinucleotide composition, and CPB. The CUB analysis of PNRSV CP sequences showed that it was not only affected by natural selection, but also affected by mutations, and natural selection played a more significant role compared to mutations as the driving force. The dinucleotide composition analysis showed an over-expression of the CpC/GpA dinucleotides and an under-expression of the UpA/GpC dinucleotides. The dinucleotide composition of the PNRSV CP gene showed a weak association with the viral lineages and hosts, but a strong association with viral codon positions. Furthermore, the CPB of PNRSV CP gene is low and is related to dinucleotide preference and codon usage patterns. This research provides reference for future research on PNRSV genetic diversity and gene evolution mechanism.

Comprehensive analysis of codon usage pattern in Eisenia fetida and its correlation with gene expression

Every individual gene or genome follows the phenomenon of codon bias, where the usage among synonymous codons is not equal. The present study was conducted to understand the CUB in E. fetida and its impact on gene expression. The genes of E. fetida were G/Cbiased, where mean of C% was highest followed by G%, T%, and A% at the third codon position. ENC plot, Neutrality plot and Parity plot analysis revealed the codon usage pattern in E. fetida was largely influenced by natural selection. Further, it was observed that CUB had a substantial negative relationship with the gene expression levels (FPKM) at p < 0.05. Altogether, these findings indicate that translational efficiency and accuracy might have modulated the choice of codon selection in the studied earthworm genome.

Uncovering a new SASH1 mutation associated with dyschromatosis universalis hereditaria using whole-exome-sequencing: A case report.

Dyschromatosis universalis hereditaria (DUH) is an uncommon form of pigmented genodermatosis that is typically inherited autosomally and dominantly. In the previous study, the pathogenic genes of DUH have been identified in ATP-binding cassette subfamily B, member 6 and SASH1. However, the mutational screening of the causative gene remains incomplete and still lacks sufficient proof in the etiology. A 2-generation Chinese family clinically diagnosed with DUH were enrolled. They showed pigmented spots from their childhood and came to the hospital for medical advice and genetic analysis. We found a novel mutation c.1757T > C (p.I586T) of SASH1 in 3 affected family members by whole-exome sequencing. Genetic outcomes and clinical examinations confirmed the diagnosis of DUH in 3 family members with lentiginous syndrome. Using whole-exome sequencing and sanger sequencing technologies, we identified a novel mutation c.1757T > C (p.I586T) of SASH1 that co-segregated in 3 afflicted family members but not in the normal individuals. Significantly, c.1757T > C (p.I586T) is a novel mutation which had not been previously reported. The same codon position in SASH1 (c.1758C > G, p.I586M) has been reported in a Japanese man, and he showed identical phenotype compared to our study participants. Our study broadens the spectrum of DUH mutations and provides more genetic characteristics of DUH in understanding its etiology. Furthermore, we demonstrated the diagnostic accuracy of whole-exome sequencing for inherited skin diseases and provided new information for etiological study.

Base composition, codon usage and patterns of gene sequence evolution in butterflies.

Coding sequence evolution is influenced by both natural selection and neutral evolutionary forces. In many species, the effects of mutation bias, codon usage and GC-biased gene conversion (gBGC) on gene sequence evolution have not been detailed. Quantification of how these forces shape substitution patterns is therefore necessary to understand the strength and direction of natural selection. Here, we used comparative genomics to investigate the association between base composition and codon usage bias on gene sequence evolution in butterflies and moths (Lepidoptera), including an in-depth analysis of underlying patterns and processes in one species, Leptidea sinapis. The data revealed significant G/C to A/T substitution bias at third codon position with some variation in the strength among different butterfly lineages. However, the substitution bias was lower than expected from previously estimated mutation rate ratios, partly due to the influence of gBGC. We found that A/T-ending codons were overrepresented in most species, but there was a positive association between the magnitude of codon usage bias and GC-content in third codon positions. In addition, the tRNA-gene population in L. sinapis showed higher GC-content at third codon positions compared to coding sequences in general and less overrepresentation of A/T-ending codons. There was an inverse relationship between synonymous substitutions and codon usage bias indicating selection on synonymous sites. We conclude that the evolutionary rate in Lepidoptera is affected by a complex interaction between underlying G/C -> A/T mutation bias and partly counteracting fixation biases, predominantly conferred by overall purifying selection, gBGC and selection on codon usage.

Chromosome-aware phylogenomics of Assassin Bugs (Hemiptera: Reduvioidea) elucidates ancient gene conflict.

Though the phylogenetic signal of loci on sex chromosomes can differ from those on autosomes, chromosomal-level genome assemblies for non-vertebrates are still relatively scarce and conservation of chromosomal gene content across deep phylogenetic scales has therefore remained largely unexplored. We here assemble a uniquely large and diverse set of samples (17 Anchored Hybrid Enrichment [AHE], 24 RNA-Seq, and 70 whole-genome sequencing [WGS] samples of variable depth) for the medically important assassin bugs (Reduvioidea). We assess the performance of genes based on multiple features (e.g., nucleotide vs. amino acid, nuclear vs. mitochondrial, and autosomal vs. X chromosomal) and employ different methods (concatenation and coalescence analyses) to reconstruct the unresolved phylogeny of this diverse (∼7,000 spp.) and old (>180 MYA) group. Our results show that genes on the X chromosome are more likely to have discordant phylogenies than those on autosomes. We find that the X chromosome conflict is driven by high gene substitution rates that impact accuracy of phylogenetic inference. However, gene tree clustering showed strong conflict even after discounting variable third codon positions. Alternative topologies were not particularly enriched for sex chromosome loci, but spread across the genome. We conclude that binning genes to autosomal or sex chromosomes may result in a more accurate picture of the complex evolutionary history of a clade.

Genetic characterization and molecular evolution of type 3 vaccine-derived polioviruses from an immunodeficient patient in China

In 2013, a case of immunodeficiency vaccine-derived poliovirus (iVDPV) was identified in Jiangxi Province, China. In this study, we purified 14 type 3 original viral isolates from this case and characterized the molecular evolution of these iVDPVs for 298 days. Genetic variants were found in most of the original viral isolates, with complex genetic and evolutionary relationships among the variants. A phylogenetic tree constructed based on the P1 region showed that these iVDPVs were classified into lineage A and B. The dominant lineage B represents a major trend in virus evolution. The nucleotide substitution rate at the third codon position (3CP) estimated by the BEAST program was 1.76×10-2 substitutions/site/year (95% HPD: 1.23-2.39×10-2). The initial OPV dose was given dating back to March 2013, which was close to the time of the last OPV vaccination, suggesting that OPV infection may have originated with the last dose of vaccine. Recombinant analysis showed that these iVDPVs were inter-vaccine recombinants with two recombination patterns, S3/S2/S1 and S3/S2/S3/S2/S1. Whole genome sequence analysis revealed that key nucleotide sites (C472U, C2034U, U2493C) associated with the attenuated phenotype of Sabin 3 have been replaced. Temperature sensitivity test showed that all tested strains were temperature-sensitive, except for the variant Day11-5. Interestingly, we observed that the variant Day11-5 temperature resistance properties may be associated with the Lys to Met substitution at the VP2-162 site. Serological test and whole genome sequence analysis showed that the seropositivity rate remained high, and mutations in the antigenic sites did not significantly alter neutralization ability.

Structural Characteristics of Mitochondrial Genomes of Eight Treehoppers (Hemiptera: Membracidae: Centrotinae) and Their Phylogenetic Implications.

Complete mitochondrial genomes were newly sequenced for eight species of the treehopper subfamily Centrotinae (Hemiptera: Membracidae), four of which represent genera for which mitogenomes were not previously available. The new mitogenomes are generally similar in overall structure, gene order, base composition, and nucleotide content to those of previously sequenced species of the subfamily. Phylogenetic analyses were conducted using both maximum likelihood and Bayesian inference methods based on three separate nucleotide sequence datasets in which RNA gene sequences and/or third codon positions were either included or excluded from the concatenated protein-coding gene alignments. The results are consistent with previous phylogenies based on morphology and partial nuclear genome data, except for the lack of support for the monophyly of Leptocentrini. These results show that mitogenome sequences are informative of both ancient and recent divergence patterns within Centrotinae.

Different Patterns of Codon Usage and Amino Acid Composition across Primate Lentiviruses.

A common feature of the mammalian Lentiviruses (family Retroviridae) is an RNA genome that contains an extremely high frequency of adenine (31.7-38.2%) while being extremely poor in cytosine (13.9-21.2%). Such a biased nucleotide composition has implications for codon usage, causing a striking difference between the frequency of synonymous codons in Lentiviruses and that in their hosts. To test whether primate Lentiviruses present differences in codon and amino acid composition, we assembled a dataset of genome sequences that includes SIV species infecting Old-World monkeys and African apes, HIV-2, and the four groups of HIV-1. Using principal component analysis, we found that HIV-1 shows a significant enrichment in adenine plus thymine in the third synonymous codon position and in adenine and guanine in the first and second nonsynonymous codon positions. Similarly, we observed an enrichment in adenine and in guanine in nonsynonymous first and second codon positions, which affects the amino acid composition of the proteins Gag, Pol, Vif, Vpr, Tat, Rev, Env, and Nef. This result suggests an effect of natural selection in shaping codon usage. Under the hypothesis that the use of synonyms in HIV-1 could reflect adaptation to that of genes expressed in specific cell types, we found a highly significant correlation between codon usage in HIV-1 and monocytes, which was remarkably higher than that with B and T lymphocytes. This finding is in line with the notion that monocytes represent an HIV-1 reservoir in infected patients, and it could help understand how this reservoir is established and maintained.

Amino acid usage and protein expression levels in the flatworm Schistosoma mansoni

Schistosoma mansoni is a parasitic flatworm that causes a human disease called schistosomiasis, or bilharzia. At the genomic level, S. mansoni is AT-rich, but has some compositional heterogeneity. Indeed, some regions of its genome are GC-rich, mainly in the regions located near the extreme ends of the chromosomes. Recently, we showed that, despite the strong bias towards A/T ending codons, highly expressed genes tend to use GC-rich codons. Here, we address the following question: are highly expressed sequences biased in their amino acid frequencies? Our analyses show that these sequences in S. mansoni, as in species ranging from bacteria to human, are strongly biased in nucleotide composition. Highly expressed genes tend to use GC-rich codons (in the first and second codon positions), which code the energetically cheapest amino acids. Therefore, we conclude that amino acid usage, at least in highly expressed genes, is strongly shaped by natural selection to avoid energetically expensive residues. Whether this is an adaptation to the parasitic way of life of S. mansoni, is unclear since the same pattern occurs in free-living species.

Codon Usage Bias Analysis in Macronuclear Genomes of Ciliated Protozoa.

Ciliated protozoa (ciliates) are unicellular eukaryotes, several of which are important model organisms for molecular biology research. Analyses of codon usage bias (CUB) of the macronuclear (MAC) genome of ciliates can promote a better understanding of the genetic mode and evolutionary history of these organisms and help optimize codons to improve gene editing efficiency in model ciliates. In this study, the following indices were calculated: the guanine-cytosine (GC) content, the frequency of the nucleotides at the third position of codons (T3, C3, A3, G3), the effective number of codons (ENc), GC content at the 3rd position of synonymous codons (GC3s), and the relative synonymous codon usage (RSCU). Parity rule 2 plot analysis, Neutrality plot analysis, ENc plot analysis, and correlation analysis were employed to explore the main influencing factors of CUB. The results showed that the GC content in the MAC genomes of each of 21 ciliate species, the genomes of which were relatively complete, was lower than 50%, and the base compositions of GC and GC3s were markedly distinct. Synonymous codon analysis revealed that the codons in most of the 21 ciliates ended with A or T and four codons were the general putative optimal codons. Collectively, our results indicated that most of the ciliates investigated preferred using the codons with anof AT-ending and that codon usage bias was affected by gene mutation and natural selection.