BACKGROUND Approximately 40%of colorectal cancer(CRC)cases are linked to Kirsten rat sarcoma viral oncogene homolog(KRAS)mutations.KRAS mutations are associated with poor CRC prognosis,especially KRAS codon 12 mutatio...BACKGROUND Approximately 40%of colorectal cancer(CRC)cases are linked to Kirsten rat sarcoma viral oncogene homolog(KRAS)mutations.KRAS mutations are associated with poor CRC prognosis,especially KRAS codon 12 mutation,which is associated with metastasis and poorer survival.However,the clinicopathological characteristics and prognosis of KRAS codon 13 mutation in CRC remain unclear.AIM To evaluate the clinicopathological characteristics and prognostic value of codonspecific KRAS mutations,especially in codon 13.METHODS This retrospective,single-center,observational cohort study included patients who underwent surgery for stage I-III CRC between January 2009 and December 2019.Patients with KRAS mutation status confirmed by molecular pathology reports were included.The relationships between clinicopathological characteristics and individual codon-specific KRAS mutations were analyzed.Survival data were analyzed to identify codon-specific KRAS mutations as recurrence-related factors using the Cox proportional hazards regression model.RESULTS Among the 2203 patients,the incidence of KRAS codons 12,13,and 61 mutations was 27.7%,9.1%,and 1.3%,respectively.Both KARS codons 12 and 13 mutations showed a tendency to be associated with clinical characteristics,but only codon 12 was associated with pathological features,such as stage of primary tumor(T stage),lymph node involvement(N stage),vascular invasion,perineural invasion,tumor size,and microsatellite instability.KRAS codon 13 mutation showed no associations(77.2%vs 85.3%,P=0.159),whereas codon 12 was associated with a lower 5-year recurrence-free survival rate(78.9%vs 75.5%,P=0.025).In multivariable analysis,along with T and N stages and vascular and perineural invasion,only codon 12(hazard ratio:1.399;95%confidence interval:1.034-1.894;P=0.030)among KRAS mutations was an independent risk factor for recurrence.CONCLUSION This study provides evidence that KRAS codon 13 mutation is less likely to serve as a prognostic biomarker than codon 12 mutation for CRC in a large-scale cohort.展开更多
Synonymous codons have different frequencies of usage in many species.Based on the frequency of usage,the codons can be divided into two groups,rare codons and abundant codons.Rare codons are found to be enriched at t...Synonymous codons have different frequencies of usage in many species.Based on the frequency of usage,the codons can be divided into two groups,rare codons and abundant codons.Rare codons are found to be enriched at the start regions of genes,and it is assumed that these codons can reduce elongation speed of genes.However,the rare codon usage in different genomic regions of mollusks and their relationship with selective pressure has not been systematically investigated.In this study,the patterns of rare codon usage are characterized at whole genome level,and their relationship with selective pressures is investigated in Crassostrea gigas.The rare codons are enriched at the start regions of genes with high and medium expression levels,and their proportion is higher than those in the genes with low expression level.The genes with longer coding sequences and more exon numbers have lower fraction of rare codons at start regions.Rare codons have lower level of nucleotide diversity and higher frequency of rare mutations at start regions.This work is the first comprehensive investigation of the relationships between rare codon usage and some intrinsic genetic factors in mollusca species.The results suggest that the selective pressures play an important role in shaping the rare codon usage in the C.gigas genome.展开更多
Codon usage is the selective and nonrandom use of synonymous codons to encode amino acids in genes for proteins. The analysis of codon usage may improve the understanding of cocion preferences between different specie...Codon usage is the selective and nonrandom use of synonymous codons to encode amino acids in genes for proteins. The analysis of codon usage may improve the understanding of cocion preferences between different species and allow to rebuild the codons of exogenous genes to increase the expression efficiency of exogenous genes, Here, codon DNA sequence （CDS） of four poplar species, including Populus tremuloides Michx., P. tomentosa Carr., P. deltoides Marsh., and P. trichocarpa Torr. ＆ Gray., is used to analyze the relative frequency of synonymous codon （RFSC）. High-frequency codons are selected by high-frequency （HF） codon analysis. The results indicate that the codon usage is common for all four poplar species and the codon preference is quite similar among the four poplar species. However, CCT encoding for Pro, and ACT coding for Thr are the preferred codons in P. tremuloides and P. tomentosa, whereas CCA coding for Pro, and ACA coding for Thr are preferred in P. deltoides and P. trichocarpa The codons such as TGC coding for Cys, TTC coding for Phe, and AAG coding for Lys, are preferred in the poplar species except P trichocarpa. GAG coding for Glu is preferred only in P deltoides, while the other three poplar species prefer to use GAA. The commonness of preferred codon allows exogenous gene designed by the preferred cocion of one of the different poplar species to be used in other poplar species.展开更多
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 Sulfol...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.展开更多
Burkholderia mallei is regarded as a potential biological weapon by the Centers for Disease Control and Prevention. In this study, the main factors shaping codon usage in the genome of B. mallei ATCC 23344 were firstl...Burkholderia mallei is regarded as a potential biological weapon by the Centers for Disease Control and Prevention. In this study, the main factors shaping codon usage in the genome of B. mallei ATCC 23344 were firstly reported. The results showed that the primary trend in codon usage variation in the B. mallei is due to translational selection; while compositional mutation bias is relatively the weaker influence and the hydrophobicity of each protein and gene length are only the minor influences. At the same time, 21 codons defined firstly as ＇optimal codons＇ might provide more useful information for the expression of target genes and development of a vaccine to prevent glanders.展开更多
Analysis of the secondary structures of mRNAs which encode mature peptides shows that the location of each codon in mRNA secondary structure has a trend, which appears to be in agreement with the conformational proper...Analysis of the secondary structures of mRNAs which encode mature peptides shows that the location of each codon in mRNA secondary structure has a trend, which appears to be in agreement with the conformational property of the corresponding amino acid to some extent. Most of the codons that encode hydrophobic amino acids are located in stable stem regions of mRNA secondary structures, and vice versa, most of the codons that encode hydrophilic amino acids are located in flexible loop regions. This result supports the recent conclusion that there may be the information transfer between the three dimensional structures of mRNA and the encoded protein.展开更多
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 oppo...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.展开更多
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...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.展开更多
Synonymous codon usage pattern presumably reflects gene expression optimization as a result of molecular evolution. Though much attention has been paid to various model organisms ranging from prokaryotes to eukaryotes...Synonymous codon usage pattern presumably reflects gene expression optimization as a result of molecular evolution. Though much attention has been paid to various model organisms ranging from prokaryotes to eukaryotes, codon usage has yet been extensively investigated for model legume Medicago truncatula. In present study, 39 531 available coding sequences （CDSs） from M. truncatula were examined for codon usage bias （CUB）. Based on analyses including neutrality plots, effective number of codons plots, and correlations between optimal codons frequency and codon adaptation index, we conclude that natural selection is a major driving force in M. truncatula CUB. We have identified 30 optimal codons encoding 18 amino acids based on relative synonymous codon usage. These optimal codons characteristically end with A or T, except for AGG and TTG encoding arginine and leucine respectively. Optimal codon usage is positively correlated with the GC content at three nucleotide positions of codons and the GC content of CDSs. The abundance of expressed sequence tag is a proxy for gene expression intensity in the legume, but has no relatedness with either CDS length or GC content. Collectively, we unravel the synonymous codon usage pattern in M. truncatula, which may serve as the valuable information on genetic engineering of the model legume and forage crop.展开更多
文摘BACKGROUND Approximately 40%of colorectal cancer(CRC)cases are linked to Kirsten rat sarcoma viral oncogene homolog(KRAS)mutations.KRAS mutations are associated with poor CRC prognosis,especially KRAS codon 12 mutation,which is associated with metastasis and poorer survival.However,the clinicopathological characteristics and prognosis of KRAS codon 13 mutation in CRC remain unclear.AIM To evaluate the clinicopathological characteristics and prognostic value of codonspecific KRAS mutations,especially in codon 13.METHODS This retrospective,single-center,observational cohort study included patients who underwent surgery for stage I-III CRC between January 2009 and December 2019.Patients with KRAS mutation status confirmed by molecular pathology reports were included.The relationships between clinicopathological characteristics and individual codon-specific KRAS mutations were analyzed.Survival data were analyzed to identify codon-specific KRAS mutations as recurrence-related factors using the Cox proportional hazards regression model.RESULTS Among the 2203 patients,the incidence of KRAS codons 12,13,and 61 mutations was 27.7%,9.1%,and 1.3%,respectively.Both KARS codons 12 and 13 mutations showed a tendency to be associated with clinical characteristics,but only codon 12 was associated with pathological features,such as stage of primary tumor(T stage),lymph node involvement(N stage),vascular invasion,perineural invasion,tumor size,and microsatellite instability.KRAS codon 13 mutation showed no associations(77.2%vs 85.3%,P=0.159),whereas codon 12 was associated with a lower 5-year recurrence-free survival rate(78.9%vs 75.5%,P=0.025).In multivariable analysis,along with T and N stages and vascular and perineural invasion,only codon 12(hazard ratio:1.399;95%confidence interval:1.034-1.894;P=0.030)among KRAS mutations was an independent risk factor for recurrence.CONCLUSION This study provides evidence that KRAS codon 13 mutation is less likely to serve as a prognostic biomarker than codon 12 mutation for CRC in a large-scale cohort.
基金supported by the National Natural Science Foundation of China(No.11701546).
文摘Synonymous codons have different frequencies of usage in many species.Based on the frequency of usage,the codons can be divided into two groups,rare codons and abundant codons.Rare codons are found to be enriched at the start regions of genes,and it is assumed that these codons can reduce elongation speed of genes.However,the rare codon usage in different genomic regions of mollusks and their relationship with selective pressure has not been systematically investigated.In this study,the patterns of rare codon usage are characterized at whole genome level,and their relationship with selective pressures is investigated in Crassostrea gigas.The rare codons are enriched at the start regions of genes with high and medium expression levels,and their proportion is higher than those in the genes with low expression level.The genes with longer coding sequences and more exon numbers have lower fraction of rare codons at start regions.Rare codons have lower level of nucleotide diversity and higher frequency of rare mutations at start regions.This work is the first comprehensive investigation of the relationships between rare codon usage and some intrinsic genetic factors in mollusca species.The results suggest that the selective pressures play an important role in shaping the rare codon usage in the C.gigas genome.
基金This work was supported by the National Major Basic Research and Development Program(No.TG1999016004)Jiangsu Provincial Natural Science Foundation(No.BK2003213).
文摘Codon usage is the selective and nonrandom use of synonymous codons to encode amino acids in genes for proteins. The analysis of codon usage may improve the understanding of cocion preferences between different species and allow to rebuild the codons of exogenous genes to increase the expression efficiency of exogenous genes, Here, codon DNA sequence （CDS） of four poplar species, including Populus tremuloides Michx., P. tomentosa Carr., P. deltoides Marsh., and P. trichocarpa Torr. ＆ Gray., is used to analyze the relative frequency of synonymous codon （RFSC）. High-frequency codons are selected by high-frequency （HF） codon analysis. The results indicate that the codon usage is common for all four poplar species and the codon preference is quite similar among the four poplar species. However, CCT encoding for Pro, and ACT coding for Thr are the preferred codons in P. tremuloides and P. tomentosa, whereas CCA coding for Pro, and ACA coding for Thr are preferred in P. deltoides and P. trichocarpa The codons such as TGC coding for Cys, TTC coding for Phe, and AAG coding for Lys, are preferred in the poplar species except P trichocarpa. GAG coding for Glu is preferred only in P deltoides, while the other three poplar species prefer to use GAA. The commonness of preferred codon allows exogenous gene designed by the preferred cocion of one of the different poplar species to be used in other poplar species.
基金The work is supported by National Natural Science Foundation of China (No. 60121101).
文摘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.
文摘Burkholderia mallei is regarded as a potential biological weapon by the Centers for Disease Control and Prevention. In this study, the main factors shaping codon usage in the genome of B. mallei ATCC 23344 were firstly reported. The results showed that the primary trend in codon usage variation in the B. mallei is due to translational selection; while compositional mutation bias is relatively the weaker influence and the hydrophobicity of each protein and gene length are only the minor influences. At the same time, 21 codons defined firstly as ＇optimal codons＇ might provide more useful information for the expression of target genes and development of a vaccine to prevent glanders.
文摘Analysis of the secondary structures of mRNAs which encode mature peptides shows that the location of each codon in mRNA secondary structure has a trend, which appears to be in agreement with the conformational property of the corresponding amino acid to some extent. Most of the codons that encode hydrophobic amino acids are located in stable stem regions of mRNA secondary structures, and vice versa, most of the codons that encode hydrophilic amino acids are located in flexible loop regions. This result supports the recent conclusion that there may be the information transfer between the three dimensional structures of mRNA and the encoded protein.
基金supported by the National Natural Science Foundation of China (31401822)
文摘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.
文摘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.
基金supported by the National Basic Research Program of China (2014CB138702)the National Natural Science Foundation of China (31502001)
文摘Synonymous codon usage pattern presumably reflects gene expression optimization as a result of molecular evolution. Though much attention has been paid to various model organisms ranging from prokaryotes to eukaryotes, codon usage has yet been extensively investigated for model legume Medicago truncatula. In present study, 39 531 available coding sequences （CDSs） from M. truncatula were examined for codon usage bias （CUB）. Based on analyses including neutrality plots, effective number of codons plots, and correlations between optimal codons frequency and codon adaptation index, we conclude that natural selection is a major driving force in M. truncatula CUB. We have identified 30 optimal codons encoding 18 amino acids based on relative synonymous codon usage. These optimal codons characteristically end with A or T, except for AGG and TTG encoding arginine and leucine respectively. Optimal codon usage is positively correlated with the GC content at three nucleotide positions of codons and the GC content of CDSs. The abundance of expressed sequence tag is a proxy for gene expression intensity in the legume, but has no relatedness with either CDS length or GC content. Collectively, we unravel the synonymous codon usage pattern in M. truncatula, which may serve as the valuable information on genetic engineering of the model legume and forage crop.
