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1.
Relationships Among Stop Codon Usage Bias, Its Context, Isochores, and Gene Expression Level in Various Eukaryotes 总被引:1,自引:0,他引:1
It is well known that stop codons play a critical role in the process of protein synthesis. However, little effort has been
made to investigate whether stop codon usage exhibits biases, such as widely seen for synonymous codon usage. Here we systematically
investigate stop codon usage bias in various eukaryotes as well as its relationships with its context, GC3 content, gene expression
level, and secondary structure. The results show that there is a strong bias for stop codon usage in different eukaryotes,
i.e., UAA is overrepresented in the lower eukaryotes, UGA is overrepresented in the higher eukaryotes, and UAG is least used
in all eukaryotes. Different conserved patterns for each stop codon in different eukaryotic classes are found based on information
content and logo analysis. GC3 contents increase with increasing complexity of organisms. Secondary structure prediction revealed
that UAA is generally associated with loop structures, whereas UGA is more uniformly present in loop and stem structures,
i.e., UGA is less biased toward having a particular structure. The stop codon usage bias, however, shows no significant relationship
with GC3 content and gene expression level in individual eukaryotes. The results indicate that genomic complexity and GC3
content might contribute to stop codon usage bias in different eukaryotes. Our results indicate that stop codons, like synonymous
codons, exhibit biases in usage. Additional work will be needed to understand the causes of these biases and their relationship
to the mechanism of protein termination.
[Reviewing Editor: Dr. Manyuan Long] 相似文献
2.
There are several sequence-dependent factors regulating gene expression. Some of them have been extensively studied, among the most prominent are GC content and codon usage bias. Other factors hypothesized to have an impact on gene expression are gene length and the thermodynamic stability of mRNA secondary structure. In this work, we analyzed two different microarray datasets of Drosophila melanogaster gene expression and one dataset of Escherichia coli. To investigate the relationship between gene expression, codon usage bias and GC content of first, second and third codon position, gene length and mRNA stability we employed a multiple regression analysis using a comprehensive linear model. It is shown that codon usage bias and GC content of the first, second and third codon position show a significant influence on gene expression, whereas no significant effect of mRNA secondary structure stability is observed. 相似文献
3.
以甜瓜蔗糖转化酶基因序列为材料,研究甜瓜蔗糖转化酶基因密码子偏好性,为改良甜瓜风味与品质提供理论依据。运用在线分析软件Codon W对甜瓜蔗糖转化酶的编码序列(Coding sequence,CDS)进行密码子分析,利用Mobyle在线工具分析同义密码子相对使用度(RSCU)、有效密码子数(ENC)、GC及GC1s、GC2s、GC3s含量。甜瓜蔗糖转化酶基因偏好于以A或T结尾的密码子。密码子ATT、GTT和AGA的RSCU值都大于1,属于共同偏好使用的密码子,而密码子GCG、CGG的RSCU值小于1,属于使用频率较低的密码子。发现密码子偏好性与亲缘关系的远近有一定的关系。要实现目的基因在外源表达系统中的成功表达和提高其表达量,可通过增加目的基因剂量,目的基因密码子优化,改善培养条件等方法实现,其中目的基因密码子优化起到了关键作用。 相似文献
4.
MJ O'Connell AM Doyle TE Juenger MT Donoghue C Keshavaiah R Tuteja C Spillane 《BMC research notes》2012,5(1):359
ABSTRACT: BACKGROUND: Synonymous codon usage bias has typically been correlated with, and attributed to translational efficiency. However, there are other pressures on genomic sequence composition that can affect codon usage patterns such as mutational biases. This study provides an analysis of the codon usage patterns in Arabidopsis thaliana in relation to gene expression levels, codon volatility, mutational biases and selective pressures. RESULTS: We have performed synonymous codon usage and codon volatility analyses for all genes in the A. thaliana genome. In contrast to reports for species from other kingdoms, we find that neither codon usage nor volatility are correlated with selection pressure (as measured by dN/dS), nor with gene expression levels on a genome wide level. Our results show that codon volatility and usage are not synonymous, rather that they are correlated with the abundance of G and C at the third codon position (GC3). CONCLUSIONS: Our results indicate that while the A. thaliana genome shows evidence for synonymous codon usage bias, this is not related to the expression levels of its constituent genes. Neither codon volatility nor codon usage are correlated with expression levels or selective pressures but, because they are directly related to the composition of G and C at the third codon position, they are the result of mutational bias. Therefore, in A. thaliana codon volatility and usage do not result from selection for translation efficiency or protein functional shift as measured by positive selection. 相似文献
5.
Sheng Zhao Qin Zhang Zhihua Chen Jincheng Zhong 《World journal of microbiology & biotechnology》2008,24(8):1585-1592
Burkholderia pseudomallei is a recognized biothreat agent and the causative agent of melioidosis. Codon usage biases of all protein-coding genes (length
greater than or equal to 300 bp) from the complete genome of B. pseudomallei K96243 have been analyzed. As B. pseudomallei is a GC-rich organism (68.5%), overall codon usage data analysis indicates that indeed codons ending in G and/or C are predominant
in this organism. But multivariate statistical analysis indicates that there is a single major trend in the codon usage variation
among the genes in this organism, which has a strong positively correlation with the expressivities of the genes. The majority
of the lowly expressed genes are scattered towards the negative end of the major axis whereas the highly expressed genes are
clustered towards the positive end. At the same time, from the results that there were two significant correlations between
axis 1 coordinates and the GC, GC3s content at silent sites of each sequence, and clearly significant negatively correlations
between the ‘Effective Number of Codons’ values and GC, GC3s content, we inferred that codon usage bias was affected by gene
nucleotide composition also. In addition, some other factors such as the lengths of the genes as well as the hydrophobicity
of genes also influence the codon usage variation among the genes in this organism in a minor way. At the same time, notably,
21 codons have been defined as ‘optimal codons’ of the B. pseudomallei. In summary, our work have provided a basic understanding of the mechanisms for codon usage bias and some more useful information
for improving the expression of target genes in vivo and in vitro.
Sheng Zhao and Qin Zhang contributed equally to this work. 相似文献
6.
Hanmei Liu Rui He Huaiyu Zhang Yubi Huang Mengliang Tian Junjie Zhang 《Molecular biology reports》2010,37(2):677-684
It is important and meaningful to understand the codon usage pattern and the factors that shape codon usage of maize. In this
study, trends in synonymous codon usage in maize have been firstly examined through the multivariate statistical analysis
on 7402 cDNA sequences. The results showed that the genes positions on the primary axis were strongly negatively correlated
with GC3s, GC content of individual gene and gene expression level assessed by the codon adaptation index (CAI) values, which
indicated that nucleotide composition and gene expression level were the main factors in shaping the codon usage of maize,
and the variation in codon usage among genes may be due to mutational bias at the DNA level and natural selection acting at
the level of mRNA translation. At the same time, CDS length and the hydrophobicity of each protein were, respectively, significantly
correlated with the genes locations on the primary axis, GC3s and CAI values. We infer that genes length and the hydrophobicity
of the encoded protein may play minor role in shaping codon usage bias. Additional 28 codons ending with a G or C base have
been defined as “optimal codons”, which may provide useful information for maize gene-transformation and gene prediction. 相似文献
7.
In this paper, the main factors shaping codon usage in the mitochondrion genome of rice were reported. Correspondence analysis, a commonly used multivariate statistical approach, was carried out to analyze synonymous codon usage bias. The results showed that the main trend was strongly correlated with the gene expression level assessed by the 'Codon Adaptation Index' value, a result that was confirmed by the distribution of genes along the first axis. From the results that there were two significant correlations between axis 1 coordinates and the GC, GC3s content at silent sites of each sequence, and clearly significant correlations between the 'Effective Number of Codons' values and GC, GC3s content, we inferred that codon usage bias was affected by gene nucleotide composition also. In addition, the hydrophobicity of each protein also played some roles in shaping codon usage in this organelle, which could be confirmed by the significant correlation between the positions of genes placed on the first axis and the hydrophobicity value of each protein. In summary, natural selection played a crucial role, nucleotide mutational bias and amino acid composition only in a minor way, in shaping codon usage in the mitochondrion genome of rice. Notably, 21 codons defined firstly as 'optimal codons' might provide some more useful information for gene engineering and/or evolution studying. 相似文献
8.
Codon reassignment to facilitate genetic engineering and biocontainment in the chloroplast of Chlamydomonas reinhardtii 下载免费PDF全文
There is a growing interest in the use of microalgae as low‐cost hosts for the synthesis of recombinant products such as therapeutic proteins and bioactive metabolites. In particular, the chloroplast, with its small, genetically tractable genome (plastome) and elaborate metabolism, represents an attractive platform for genetic engineering. In Chlamydomonas reinhardtii, none of the 69 protein‐coding genes in the plastome uses the stop codon UGA, therefore this spare codon can be exploited as a useful synthetic biology tool. Here, we report the assignment of the codon to one for tryptophan and show that this can be used as an effective strategy for addressing a key problem in chloroplast engineering: namely, the assembly of expression cassettes in Escherichia coli when the gene product is toxic to the bacterium. This problem arises because the prokaryotic nature of chloroplast promoters and ribosome‐binding sites used in such cassettes often results in transgene expression in E. coli, and is a potential issue when cloning genes for metabolic enzymes, antibacterial proteins and integral membrane proteins. We show that replacement of tryptophan codons with the spare codon (UGG→UGA) within a transgene prevents functional expression in E. coli and in the chloroplast, and that co‐introduction of a plastidial trnW gene carrying a modified anticodon restores function only in the latter by allowing UGA readthrough. We demonstrate the utility of this system by expressing two genes known to be highly toxic to E. coli and discuss its value in providing an enhanced level of biocontainment for transplastomic microalgae. 相似文献
9.
Stenøien HK 《Heredity》2005,94(1):87-93
Patterns of codon usage bias were studied in the moss model species Physcomitrella patens. A total of 92 nuclear, protein coding genes were employed, and estimated levels of gene expression were tested for association with two measures of codon usage bias and other variables hypothesized to be associated with gene expression. Codon bias was found to be positively associated both with estimated levels of gene expression and GC content in the coding parts of studied genes. However, GC content in noncoding parts, that is, introns and 5' and 3' untranslated regions (UTRs), was not associated with estimated levels of gene expression. It is argued that codon bias is not shaped by mutational bias, but rather by weak natural selection for translational efficiency in P. patens. The possible role of life history characteristics in shaping patterns of codon usage in this species is discussed. 相似文献
10.
In some Drosophila species, there are two types of greatly diverged amylase (Amy) genes (Amy clusters 1 and 2), each encoding active amylase isozymes. Cluster 1 is located at the middle of its chromosomal arm, and the region has a normal local recombination rate. However, cluster 2 is near the centromere, and this region is known to have a reduced recombination rate. Although nonsynonymous substitutions follow a molecular clock, synonymous substitutions were accelerated in cluster 2 after gene duplications. This resulted in a higher GC content at the third codon position (GC3) and codon usage bias in cluster 1, and lower GC3 content and codon usage bias in the cluster 2. However, no systematic difference in GC content was observed in the first and second codon positions or the 3'-flanking regions. Therefore, differences in local recombination rate rather than mutation bias might explain the divergence at synonymous sites between the two Amy clusters within species (Hill-Robertson effect). Alternatively, the different patterns and levels of expression between the two clusters may imply that the reduced expression level in cluster 2 caused by chromatin potentiation decreased the codon bias. Both of these hypotheses imply the importance of the genomic background as a driving force of divergence between non-tandemly duplicated genes. 相似文献
11.
Background: Oncogenes are the genes that have the potential to induce cancer. The extent and origin of codon usage bias is an
important indicator of the forces shaping genome evolution in living organisms. Results: We observed moderate correlations
between gene expression as measured by CAI and GC content at any codon site. The findings of our results showed that there is a
significant positive correlation (Spearman''s r= 0.45, P<0.01) between GC content at first and second codon position with that of
third codon position. Further, striking negative correlation (r = -0.771, P < 0.01) between ENC with the GC3s values of each gene
and positive correlation (r=0.644, P<0.01) in between CAI and ENC was also observed. Conclusions: The mutation pressure is the
major determining factor in shaping the codon usage pattern of oncogenes rather than natural selection since its effects are present
at all codon positions. The results revealed that codon usage bias determines the level of oncogene expression in human. Highly
expressed oncogenes had rich GC contents with high degree of codon usage bias. 相似文献
12.
We have analyzed codon usage patterns of 70 sequenced genes from different Lactobacillus species. Codon usage in lactobacilli is highly biased. Both inter-species and intra-species heterogeneity of codon usage bias was observed. Codon usage in L. acidophilus is similar to that in L. helveticus, but dissimilar to that in L. bulgaricus, L. casei, L. pentosus and L. plantarum. Codon usage in the latter three organisms is not significantly different, but is different from that in L. bulgaricus. Inter-species differences in codon usage can, at least in part, be explained by differences in mutational drift. L. bulgaricus shows GC drift, whereas all other species show AT drift. L. acidophilus and L. helveticus rarely use NNG in family-box (a set of synonymous) codons, in contrast to all other species. This result may be explained by assuming that L. acidophilus and L. helveticus, but not other species examined, use a single tRNA species for translation of family-box codons. Differences in expression level of genes are positively correlated with codon usage bias. Highly expressed genes show highly biased codon usage, whereas weakly expressed genes show much less biased codon usage. Codon usage patterns at the 5'-end of Lactobacillus genes is not significantly different from that of entire genes. The GC content of codons 2-6 is significantly reduced compared with that of the remainder of the gene. The possible implications of a reduced GC content for the control of translation efficiency are discussed. 相似文献
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14.
Recent studies have suggested that the thermodynamic stability of mRNA secondary structure near the start codon can regulate translation efficiency in Escherichia coli, and that translation is more efficient the less stable the secondary structure. We survey the complete genomes of 340 species for signals of reduced mRNA secondary structure near the start codon. Our analysis includes bacteria, archaea, fungi, plants, insects, fishes, birds, and mammals. We find that nearly all species show evidence for reduced mRNA stability near the start codon. The reduction in stability generally increases with increasing genomic GC content. In prokaryotes, the reduction also increases with decreasing optimal growth temperature. Within genomes, there is variation in the stability among genes, and this variation correlates with gene GC content, codon bias, and gene expression level. For birds and mammals, however, we do not find a genome-wide trend of reduced mRNA stability near the start codon. Yet the most GC rich genes in these organisms do show such a signal. We conclude that reduced stability of the mRNA secondary structure near the start codon is a universal feature of all cellular life. We suggest that the origin of this reduction is selection for efficient recognition of the start codon by initiator-tRNA. 相似文献
15.
In many unicellular organisms, invertebrates, and plants, synonymous codon usage biases result from a coadaptation between
codon usage and tRNAs abundance to optimize the efficiency of protein synthesis. However, it remains unclear whether natural
selection acts at the level of the speed or the accuracy of mRNAs translation. Here we show that codon usage can improve the
fidelity of protein synthesis in multicellular species. As predicted by the model of selection for translational accuracy,
we find that the frequency of codons optimal for translation is significantly higher at codons encoding for conserved amino
acids than at codons encoding for nonconserved amino acids in 548 genes compared between Caenorhabditis elegans and Homo sapiens. Although this model predicts that codon bias correlates positively with gene length, a negative correlation between codon
bias and gene length has been observed in eukaryotes. This suggests that selection for fidelity of protein synthesis is not
the main factor responsible for codon biases. The relationship between codon bias and gene length remains unexplained. Exploring
the differences in gene expression process in eukaryotes and prokaryotes should provide new insights to understand this key
question of codon usage.
Received: 18 June 2000 / Accepted: 10 November 2000 相似文献
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17.
Héctor Musto Héctor Romero Helena Rodríguez-Maseda 《Journal of molecular evolution》1998,46(2):159-167
Synonymous codon choices vary considerably among Schistosoma mansoni genes. Principal components analysis detects a single major trend among genes, which highly correlates with GC content in
third codon positions and exons, but does not discriminate among putatively highly and lowly expressed genes. The effective
number of codons used in each gene, and its distribution when plotted against GC3, suggests that codon usage is shaped mainly by mutational biases. The GC content of exons, GC3, 5′, 3′, and flanking (5′+ 3′+ introns) regions are all correlated among them, suggesting that variations in GC content may
exist among different regions of the S. mansoni genome. We propose that this genome structure might be among the most important factors shaping codon usage in this species,
although the action of selection on certain sequences cannot be excluded.
Received: 10 March 1997 / Accepted: 27 June 1997 相似文献
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19.
Evolution of chromosome bands: Molecular ecology of noncoding DNA 总被引:25,自引:0,他引:25
Gerald P. Holmquist 《Journal of molecular evolution》1989,28(6):469-486
Summary Giemsa dark bands, G-bands, are a derived chromatin character that evolved along the chromosomes of early chordates. They
are facultative heterochromatin reflecting acquisition of a late replication mechanism to repress tissue-specific genes. Subsequently,
R-bands, the primitive chromatin state, became directionally GC rich as evidenced by Q-banding of mammalian and avian chromosomes.
Contrary to predictions from the neutral mutation theory, noncoding DNA is positionally constrained along the banding pattern
with short interspersed repeats in R-bands and long interspersed repeats in G-bands. Chromosomes seem dynamically stable:
the banding pattern and gene arrangement along several human and murine autosomes has remained constant for 100 million years,
whereas much of the noncoding DNA, especially retroposons, has changed. Several coding sequence attributes and probably mutation
rates are determined more by where a gene lives than by what it does. R-band exons in homeotherms but not G-band exons have
directionally acquired GC-rich wobble bases and the corresponding codon usage: CpG islands in mammals are specific to R-band
exons, exons not facultatively heterochromatinized, and are independent of the tissue expression pattern of the gene. The
dynamic organization of noncoding DNA suggests a feedback loop that could influence codon usage and stabilize the chromosome’s
chromatin pattern: DNA sequences determine affinities of → proteins that together form → a chromatin that modulates → rate
constants for DNA modification that determine → DNA sequences. Theories of hierarchical selection and molecular ecology show
how selection can act on Darwinian units of noncoding DNA at the genome level thus creating positionally constrained DNA and
contributing minimal genetic load at the individual level.
Presented in part at the FEBS Symposium on Genome Organization and Evolution, held in Crete, Greece, September 1–5, 1986 相似文献
20.