Analysis of Synonymous Codon Usage in Aeropyrum pernix K1 and Other Crenarchaeota Microorganisms

In this study, a comparative analysis of the codon usage bias was performed in Aeropyrum pernix K1 and two other phylogenetically related Crenarchaeota microorganisms （i.e., Pyrobaculum aerophilum str. IM2 and Sulfolobus acidocaldarius DSM 639）. The results indicated that the synonymous codon usage in A. pernix K1 was less biased, which was highly correlated with the GC3s value. The codon usage patterns were phylogenetically conserved among these Crenarchaeota microorganisms. Comparatively, it is the species function rather than the gene function that determines their gene codon usage patterns. A. pernix K1, P. aerophilum str. IM2, and S. acidocaldarius DSM 639 live in differently extreme conditions. It is presumed that the hving environment played an important role in determining the codon usage pattern of these microorganisms. Besides, there was no strain-specific codon usage among these microorganisms. The extent of codon bias in A. pernix K1 and S. acidocaldarius DSM 639 were highly correlated with the gene expression level, but no such association was detected in P. aerophilum str. IM2 genomes.

Genome-wide analysis of the synonymous codon usage patterns in apple

Apple（Malus×domestica） has been proposed as an important woody plant and the major cultivated fruit trees in temperate regions. Apple whole genome sequencing has been completed, which provided an excellent opportunity for genome-wide analysis of the synonymous codon usage patterns. In this study, a multivariate bioinformatics analysis was performed to reveal the characteristics of synonymous codon usage and the main factors affecting codon bias in apple. The neutrality, correspondence, and correlation analyses were performed by Codon W and SPSS（Statistical Product and Service Solutions） programs, indicating that the apple genome codon usage patterns were affected by mutational pressure and selective constraint. Meanwhile, coding sequence length and the hydrophobicity of proteins could also influence the codon usage patterns. In short, codon usage pattern analysis and determination of optimal codons has laid an important theoretical basis for genetic engineering, gene prediction and molecular evolution studies in apple.

Synonymous codon usage in Methanosarcina mazei str.Goe1 and other Euryarchaeota microorganisms

A comparative analysis of the codon usage bias was conducted in Methanosarcina mazei str. Goel and two related Euryarchaeota microorganisms （Picrophilus torridus str. DSM 9790 and Natronomonas pharaonis str. DSM 2160）. Results revealed that synonymous codon usage in Methanosarcina mazei str. Goel was less biased, which was highly correlated with the GC3S value. And the codon usage patterns were phylogenetically conserved among those Euryarchaeota microorganisms. By employing a hierarchical clustering analysis, it can be seen that it is more the species than the gene function that determines their gene codon usage pattems. Considering that those microorganisms live in different environments where the pH conditions vary quite a lot, it can be presumed that their living environments, especially the pH conditions, play an important role in determining those microorganisms＇ codon usage pattems.

A Presumed Synonymous Mutation of PKD2 Caused Autosomal Dominant Polycystic Kidney Disease in a Chinese Family

Objective:Autosomal dominant polycystic kidney disease(ADPKD)is mainly caused by the pathogenic mutation of PKD1 or PKD2 gene and usually affects bilateral kidneys.Synonymous mutations are generally assumed to be neutral as they do not alter amino acids.Herein,we described an extremely rare ADPKD child caused by a heterozygous synonymous mutation of PKD2 gene accompanied by massive proteinuria and congenital solitary kidney.Methods:Clinical characteristics of the patients were summarized.Whole-exome sequencing was performed to screen the disease-causing gene mutation,and reverse transcription polymerase chain reaction(RT-PCR)and Sanger sequencing were applied to analyze the impact of the identified mutation on gene transcription and splicing.Results:Polycystic changes were found in the solitary kidney of a girl initially presented with nephrotic-range proteinuria.Thereafter her mother and 2 other family members were diagnosed to be ADPKD.Whole-exome sequencing of the proband identified a heterozygous synonymous mutation(c.1716G>A,p.Lys572=)located in the splicing site of exon 7 in PKD2 gene,which was co-segregated with the PKD phenotype in the family.RT-PCR and direct sequencing of amplified products revealed that this heterozygous synonymous mutation led to exon7 skipping in PKD2 gene.Conclusion:We reported an extremely rare child case of ADPKD2 in combination with solitary kidney and nephrotic-range proteinuria,and firstly confirmed the pathogenicity of a heterozygous synonymous mutation(c.1716G>A)in PKD2 gene.The results indicate that synonymous mutations should not be excluded from disease-causing if they are located in splicing site of an exon.

Evolutionary selection on synonymous codons in RNA G-quadruplex structural region

To investigate how synonymous codons have been adapted to the formation of ribonucleic acid(RNA)G-quadruplex(rG4)structure,a computational searching algorithm G4Hunter was applied to detect rG4 structures in protein-coding sequences of mRNAs in five eukaryotic species.The native sequences forming rG4s were then compared with randomized sequences to evaluate selection on synonymous codons.Factors that may influence the formation of rG4 were also investigated,and the selection pressures of rG4 in different gene regions were compared to explore its potential roles in gene regulation.The results show universal selective pressure acts on synonymous codons in rG4 regions to facilitate rG4 formation in five eukaryotic organisms.While G-rich codon combinations are preferred in the rG4 structural region,C-rich codon combinations are selectively unfavorable for rG4 formation.Gene's codon usage bias,nucleotide composition,and evolutionary rate can account for the selective variations on synonymous codons among rG4 structures within a species.Moreover,rG4 structures in the translational initiation region showed significantly higher selective pressures than those in the translational elongation region.

Acquiring synonymous attribute phrases for named entities via online encyclopedia

In this work,an approach is proposed to acquire synonymous attribute phrases of named entities(NEs) from an online encyclopedia.Synonymous attribute phrases are the phrases that express the same attribute with different surface forms for a class of NEs.Specifically,the proposed approach is composed of three stages.Firstly,the entries related to a given NE class are automatically selected from an online encyclopedia.Secondly,attribute phrases are extracted based on the statistics of phrase frequency.Thirdly,synonymous attributes are identified in a pairwise manner through a classification framework combining multiple features.The proposed approach is applied on Baidu Baike,a Chinese online encyclopedia,for four different NE classes.Experimental results show that the approach obtains an average precision of 74%and an average F-value of 65%for the four NE classes.In particular,thousands of synonymous attribute phrase pairs are acquired for each class,which demonstrates the effectiveness of the proposed approach.

A Synonymous Polymorphism of APCDD1 Affects Translation Efficacy and is Associated with Androgenic Alopecia

The APCDDI （adenomatosis polyposis coli down-regulated 1） gene is an inhibitor of the Wnt signaling pathway, and a rare mutation of this gene has been associated with hereditary hypotrichosis simplex. In this study, the authors aimed to investigate whether common APCDD1 gene polymorphisms contribute to the development of androgenic alopecia. Patients （n = 210） with androgenic alopecia and 98 controls were investigated. SNPs （Single nucleotide polymorphisms） in the coding region of the gene were sequenced. A significant difference in genotype distribution was found for the c. 1781C/T, p.L476L SNP （rs3185480） of the APCDD1 gene. This SNP is located in exon 5 and is associated with a 3.5- and a 2.8-fold increase in risk for the development of androgenic alopecia for homozygote （CI 0.933-13.125; nominal regression P = 0.063） and heterozygote （CI 1.086-7.217; nominal regression P = 0.033） carriers, respectively. These data suggest that the rs3185480 polymorphism contributes to the development of androgenic alopecia. Protein expression experiments revealed that the polymorphism is associated with reduced APCDDI protein abundance. This reduction is likely due to altered codon usage for leucine from a preferred codon （CTC） to a rare codon （CTT）, which might influence translation efficiency and, thus, APCDDI protein level.

Delayed-onset adenosine deaminase deficiency with a novel synonymous mutation and a case series from China

Background Adenosine deaminase(ADA)is a key enzyme in the purine salvage pathway.Genetic defects of the ADA gene can cause a subtype of severe combined immunodeficiency.To date,few Chinese cases have been reported.Methods We retrospectively reviewed the medical records of patients diagnosed with ADA deficiency in Beijing Children's Hospital and summarized the previously published ADA deficiency cases from China in the literature.Results Nine patients were identified with two novel mutations(W272X and Q202=).Early-onset infection,thymic abnor-malities and failure to thrive were the most common manifestations of Chinese ADA-deficient patients.The ADA genotype has a major effect on the clinical phenotype.Notably,a novel synonymous mutation(c.606G>A,p.Q202=)was identified in a delayed-onset patient,which affected pre-mRNA splicing leading to a frameshift and premature truncation of the protein.Furthermore,the patient showed γδT cells expansion with an increased effect or phenotype,which may be associated with the delayed onset of disease.In addition,we reported cerebral aneurysm and intracranial artery stenosis for the first time in ADA deficiency.Five patients died with a median age of four months,while two patients received stem cell transplantation and are alive.Conclusions This study described the first case series of Chinese ADA-deficient patients.Early-onset infection,thymic abnormalities and failure to thrive were the most common manifestations in our patients.We identified a synonymous muta-tion that affected pre-mRNA splicing in the ADA gene,which had never been reported in ADA deficiency.Furthermore,we reported cerebral aneurysm in a delayed-onset patient for the first time.Further study is warranted to investigate the underlying mechanisms.

Traditional Chinese Medicine Synonymous Term Conversion:A Bidirectional Encoder Representations from Transformers-Based Model for Converting Synonymous Terms in Traditional Chinese Medicine

Background:The medical records of traditional Chinese medicine(TCM)contain numerous synonymous terms with different descriptions,which is not conducive to computer-aided data mining of TCM.However,there is a lack of models available to normalize synonymous TCM terms.Therefore,construction of a synonymous term conversion(STC)model for normalizing synonymous TCM terms is necessary.Methods:Based on the neural networks of bidirectional encoder representations from transformers(BERT),four types of TCM STC models were designed:Models based on BERT and text classification,text sequence generation,named entity recognition,and text matching.The superior STC model was selected on the basis of its performance in converting synonymous terms.Moreover,three misjudgment inspection methods for the conversion results of the STC model based on inconsistency were proposed to find incorrect term conversion:Neuron random deactivation,output comparison of multiple isomorphic models,and output comparison of multiple heterogeneous models(OCMH).Results:The classification-based STC model outperformed the other STC task models.It achieved F1 scores of 0.91,0.91,and 0.83 for performing symptoms,patterns,and treatments STC tasks,respectively.The OCMH method showed the best performance in misjudgment inspection,with wrong detection rates of 0.80,0.84,and 0.90 in the term conversion results for symptoms,patterns,and treatments,respectively.Conclusion:The TCM STC model based on classification achieved superior performance in converting synonymous terms for symptoms,patterns,and treatments.The misjudgment inspection method based on OCMH showed superior performance in identifying incorrect outputs.

Evaluation of Six Methods for Estimating Synonymous and Non-synonymous Substitution Rates

Methods for estimating synonymous and nonsynonymous substitution rates among protein-coding sequences adopt different mutation (substitution) models with subtle yet significant differences, which lead to different estimates of evolutionary information. Little attention has been devoted to the comparison of methods for obtaining reliable estimates since the amount of sequence variations within targeted datasets is always unpredictable. To our knowledge, there is little information available in literature about evaluation of these different methods. In this study, we compared six widely used methods and provided with evaluation results using simulated sequences. The results indicate that incorporating sequence features (such as transition/transversion bias and nucleotide/codon frequency bias) into methods could yield better performance. We recommend that conclusions related to or derived from Ka and Ks analyses should not be readily drawn only according to results from one method.

Is there a close relationship between synonymous codon bias and codon-anticodon binding strength in human genes?

Synonymous codon bias has been examined in 78 human genes (19967 codons) and measured by relative synonymous codon usage (RSCU). Relative frequencies of all kinds of dinucleotides in 2,3 or 3,4 codon positions have been calculated, and codon-anticodon binding strength has been estimated by the stacking energies of codon-anticodon bases in Watson-Crick pairs. The data show common features in synonymous codon bias for all codon families in human genes: all C-ending codons, which possess the strongest codon-anticodon binding energies, are the most favored codons in almost all codon families, and those codons with medium codon-anticodon binding energies are avoided. Data analysis suggests that besides isochore and genome signature, codon-anticodon binding strength may be closely related to synonymous codon choice in human genes. The join-effect of these factors on human genes results in the common features in codon bias.

A single synonymous mutation determines the phosphorylation and stability of the nascent protein

p53 is an intrinsically disordered protein with a large number of post-translational modifications and interacting partners.The hierarchical order and subcellular location of these events are still poorly understood.The activation of p53 during the DNA damage response(DDR)requires a switch in the activity of the E3 ubiquitin ligase MDM2 from a negative to a positive regulator of p53.This is mediated by the ATM kinase that regulates the binding of MDM2 to the p53 mRNA facilitating an increase in p53 synthesis.Here we show that the binding of MDM2 to the p53 mRNA brings ATM to the p53 polysome where it phosphorylates the nascent p53 at serine 15 and prevents MDM2-mediated degradation of p53.A single synonymous mutation in p53 codon 22(L22L)prevents the phosphorylation of the nascent p53 protein and the stabilization of p53 following genotoxic stress.The ATM trafficking from the nucleus to the p53 polysome is mediated by MDM2,which requires its interaction with the ribosomal proteins RPL5 and RPL11.These results show how the ATM kinase phosphorylates the p53 protein while it is bang synthesized and offer a novel mechanism whereby a single synonymous mutation controls the stability and activity of the encoded protein.

HOW CORPUS-BASED APPROACH CAN CONTRIBUTE TO THE STUDY OF SEEMINGLY SYNONYMOUS WORDS

In the English language, there are many words which are considered synonymous in that dictionaries and thesauruses often define them in identical meanings. Under such circumstances, EFL learners are confronted with a big difficulty in acquiring these words of similar meanings. They often regard synonymous words as equivalents and use them alternately, which sometimes result in ambiguity or awkwardness of their language. However, with the advent of corpora and concordancing programs, a new way of investigating and learning English synonymous words has emerged. This paper explores colligational patterns, collocational behavior and semantic prosody of two seemingly synonymous verbs, gain and obtain, in two native speaker corpora, the Brown Corpus and the LOB Corpus, in order to show how these 'equivalencies' can be misleading because 'synonymous' words are typically used in different ways. The study also examines EFL learners' behavior in using synonymous words by investigating the Chinese Learner English Corpus (CLEC). From the results of the study, it can be seen that Chinese EFL learners have not yet acquired a full understanding of the usage of gain and obtain with respect to colligation, collocation and semantic prosody. Their underuses and overuses of some grammatical forms and lexical patterns of the two target synonymous words might be influenced either by their mother tongue or by the registers of their English writing or by both. The paper finally discusses the implications of corpus-based study in vocabulary teaching and learning in general.

A Corpus-Driven Perspective on the Verb Valency Structure of Chinese EFL Learners:A Case Study of“Suggest”and“Advise”

This paper investigates the verb valency structure of English that is used by English as Foreign Language(EFL)learners from a corpus-driven perspective.Specifically,it focuses on the usage of the verbs“suggest”and“advise”in a selected corpus.By analyzing a sample of written and spoken texts,this study attempts to investigate the similarities and differences in the patterns of verb valency between native English speakers and Chinese EFL learners.The findings of this research can contribute to a better understanding of the challenges faced by Chinese EFL learners in acquiring accurate verb valency structures and provide insights for language teachers in designing effective pedagogical approaches.

Type-2 Diabetes Mellitus and Glucagon-Like Peptide-1 Receptor toward Predicting Possible Association

Aim: This study aimed to investigate the effect of non-synonymous SNPs (nsSNPs) of the Glucagon-like peptide-1 Receptor (GLP-1R) gene in protein function and structure using different computational software. Introduction: The GLP1R gene provides the necessary instruction for the synthesis of the insulin hormones which is needed for glucose catabolism. Polymorphisms in this gene are associated with diabetes. The protein is an important drug target for the treatment of type-2 diabetes and stroke. Material and Methods: Different nsSNPs and protein-related sequences were obtained from NCBI and ExPASY database. Gene associations and interactions were predicted using GeneMANIA software. Deleterious and damaging effects of nsSNPs were analyzed using SIFT, Provean, and Polyphen-2. The association of the nsSNPs with the disease was predicted using SNPs & GO software. Protein stability was investigated using I-Mutant and MUpro software. The structural and functional impact of point mutations was predicted using Project Hope software. Project Hope analyzes the mutations according to their size, charge, hydrophobicity, and conservancy. Results: The GLP1R gene was found to have an association with 20 other different genes. Among the most important ones is the GCG (glucagon) gene which is also a trans membrane protein. Overall 7229 variants were seen, and the missense variants or nsSNPs (146) were selected for further analysis. The total number of nsSNPs obtained in this study was 146. After being subjected to SIFT software (27 Deleterious and 119 Tolerated) were predicted. Analysis with Provean showed that (20 deleterious and 7 neutral). Analysis using Polyphen-2 revealed 17 probably damaging, 2 possibly damaging and 1 benign nsSNPs. Using two additional software SNPs & GO and PHD-SNPs showed that 14 and 17 nsSNPs had a disease effect, respectively. Project Hope software predicts the effect of the 14 nsSNPs on the protein function due to differences in charge, size, hydrophobicity, and conservancy between the wild and mutant types. Conclusion: In this study, the 14 nsSNPs which were highly affected the protein function. This protein is providing the necessary instruction for the synthesis of the insulin hormones which is needed for glucose catabolism. Polymorphisms in this gene are associated with diabetes and also affect the treatment of diabetic patients due to the fact that the protein acts as an important drug target.

A Comparative Study of the Usage of Synonyms Based on BNC-Taking Assessment and Evaluation as Examples

The discrimination of synonyms has always been one of the great challenges for English learners.Taking assessment and evaluation as examples,this study analyses the similarities and differences of the two words,as well as their usage from the perspectives of frequency,stylistics,collocation and semantic prosody with the help of British National Corpus,and demonstrates the importance of corpus retrieval tools in synonyms discrimination.Furthermore,this paper will give some suggestions for English learners and teachers in English vocabulary teaching.

Melanocortin-1 receptor gene variants in four Chinese ethnic populations

There is strong relationship between melanocortin-1 receptor (MCIR) gene variants and human hair color and skin type. Based on a sequencing study of MC1R gene in 50 individuals from the Uygur, Tibetan, Wa and Dai ethnic populations, we discuss the occurrence of 7 mc1r variants consisting of 5 nonsynonymous sites (Val60Leu, Arg67Gln, Val92Met, Arg163Gln and Ala299Val) and 2 synonymous sites (C414T and A942G), among which C414T and Ala299Val were reported for the first time. Confirmation and analysis were the made of 122 individuals at three common point mutations (Val92Met, Arg163Gln, A942G) using PCR-SSCP. The frequency of Arg163Gln variant varies in the four ethnic populations, with percentage of 40%, 85.0%, 66. 2% and 72.7%, respectively, while those of Val92Met and A942G are roughly similar in these four populations. The different environments, migration and admixture of various ethnic groups in China might have impact on the observed frequency of Arg163Gln.

Covariation of mutation pairs expressed in HIV-1 protease and reverse transcriptase genes subjected to varying treatments

A previous study, focused on the correlation of muta-tion pairs of synonymous (S) and asynonymous (A) mutations, distinguished only between the treated and untreated data of protease and reverse tran-scriptase (RT) of HIV-1 subtype B. It is well known that single mutation patterns in HIV-1 are treat-ment-specific. It logically follows that covariation between mutations will also be treatment specific. Thus, our motivation is to give a more in depth study of the covariation between mutation pairs, analyzing not only treated and untreated, but what specific treatments were used, and how they affected the co-variation between the mutations differently. We in-tended to further deepen this study by analyzing the covariation of mutations in protease and RT in dif-ferent subtypes of HIV-1. We found that virus sam-ples subjected to antiretroviral Protease- and RT- inhibitors do show different patterns of mutation covariation in B-subtype protease and RT of HIV-1, while maintaining the same overall trend. covariation will tend to be higher and more distinct from and covariation after treatment. The same trend continues in protease and RT re-gardless of subtype. We also found the highly cova-ried codon positions, position pairs, and position- covariation clusters in protease, affected by different treatments. Most of them are well known major drug-resistance sites for these treatments.

Title>A Review of the Genus uscoptilia Arenberger(Lepidoptera: Pterophoridae)

The genus Fuscoptilia is reviewed in this paper. Fuscoptilia hoenei Arenberger, a new synonym of Fuscoptilia sinuata (Qin & Zheng), is established. The females of Fuscoptilia sinuata (Qin & Zheng) and Fuscoptilia jarosi Arenberger are described for the first time in science. The adults are photographed, and the male and female genital structures are figured. A key to the described species in the world is given.

Analysis of Codon Usage Pattern of Banana Basic Secretory Protease Gene

[Objective] The objective of this study was to understand the codon usage bias pattern of banana pathogenesis-related 17 gene, Basic Secretory Protease gene(MaBSP). [Method] Relative codon usage patterns of MaBSP were calculated using the software CodonW version 1.4.2. and the web-based tool(http://kazusa.or.jp/codon/).[Result] Our findings showed that C-ended and G-ended codons were the most preferential except the TER codon UGA which was coded for by just one codon. The ENc value, relationship between AT bias and GC bias, Random synonymous codon usage(RSCU) and CAI all showed that codon bias usage existed in MaBSP gene.[Conclusion] The codon usage patterns of MaBSP gene is principally influenced by natural selection in the third position. However, other multiple factors also influence this pattern.