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1.
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
2.
The Nonrandom Location of Synonymous Codons Suggests That Reading Frame-Independent Forces Have Patterned Codon Preferences 总被引:6,自引:0,他引:6
Biased codon usage is common in eukaryotic and prokaryotic genes. Evidence from Escherichia, Saccharomyces, and Drosophila indicates that it favors translational efficiency and accuracy. However, to date no functional advantages have been identified
in the codon–anticodon interactions involving the most frequently used (preferred) codons. Here we present evidence that forces
not related to the individual codon–anticodon interaction may be involved in determining which synonymous codons are preferred
or avoided. We show that the ``off-frame' trinucleotide motif preferences inferrable from Drosophila coding regions are often in the same direction as Drosophila's ``in-frame' codon preferences, i.e., its codon usage. The off-frame preferences were inferred from the nonrandomness of
the location of confamilial synonymous codons along coding regions—a pattern often described as a context dependence of nucleotide
choice at synonymous positions or as codon-pair bias. We relied on randomizations of the location of confamilial codons that
do not alter, and cannot be influenced by, the encoded amino acid sequences, codon usage, or base composition of the genes
examined. The statistically significant congruency of in-frame and off-frame trinucleotide preferences suggests that the same
kind of reading-frame-independent force(s) may also influence synonymous codon choice. These forces may have produced biases
in codon usage that then led to the evolution of the translational advantages of these motifs as preferred codons. Under this
scenario, tRNA pool size differences between preferred and nonpreferred codons initially were evolved to track the default
overrepresentation of codons with preferred motifs. The motif preference hypothesis can explain the structuring of codon preferences
and the similarities in the codon usages of distantly related organisms.
Received: 10 November 1998 / Accepted: 23 February 1999 相似文献
3.
4.
Susanta K. Behura David W. Severson 《Biological reviews of the Cambridge Philosophical Society》2013,88(1):49-61
Codon usage bias refers to the phenomenon where specific codons are used more often than other synonymous codons during translation of genes, the extent of which varies within and among species. Molecular evolutionary investigations suggest that codon bias is manifested as a result of balance between mutational and translational selection of such genes and that this phenomenon is widespread across species and may contribute to genome evolution in a significant manner. With the advent of whole‐genome sequencing of numerous species, both prokaryotes and eukaryotes, genome‐wide patterns of codon bias are emerging in different organisms. Various factors such as expression level, GC content, recombination rates, RNA stability, codon position, gene length and others (including environmental stress and population size) can influence codon usage bias within and among species. Moreover, there has been a continuous quest towards developing new concepts and tools to measure the extent of codon usage bias of genes. In this review, we outline the fundamental concepts of evolution of the genetic code, discuss various factors that may influence biased usage of synonymous codons and then outline different principles and methods of measurement of codon usage bias. Finally, we discuss selected studies performed using whole‐genome sequences of different insect species to show how codon bias patterns vary within and among genomes. We conclude with generalized remarks on specific emerging aspects of codon bias studies and highlight the recent explosion of genome‐sequencing efforts on arthropods (such as twelve Drosophila species, species of ants, honeybee, Nasonia and Anopheles mosquitoes as well as the recent launch of a genome‐sequencing project involving 5000 insects and other arthropods) that may help us to understand better the evolution of codon bias and its biological significance. 相似文献
5.
Summary We examined the codon usages in wellconserved and less-well-conserved regions of vertebrate protein genes and found them to be similar. Despite this similarity, there is a statistically significant decrease in codon bias in the less-well-conserved regions. Our analysis suggests that although those codon changes initially fixed under amino acid replacements tend to follow the overall codon usage pattern, they also reduce the bias in codon usage. This decrease in codon bias leads one to predict that the rate of change of synonymous codons should be greater in those regions that are less well conserved at the amino acid level than in the better-conserved regions. Our analysis supports this prediction. Furthermore, we demonstrate a significantly elevated rate of change of synonymous codons among the adjacent codons 5 to amino acid replacement positions. This provides further support for the idea that there are contextual constraints on the choice of synonymous codons in eukaryotes. 相似文献
6.
In bacteria, synonymous codon usage can be considerably affected by base composition at neighboring sites. Such context-dependent
biases may be caused by either selection against specific nucleotide motifs or context-dependent mutation biases. Here we
consider the evolutionary conservation of context-dependent codon bias across 11 completely sequenced bacterial genomes. In
particular, we focus on two contextual biases previously identified in Escherichia coli; the avoidance of out-of-frame stop codons and AGG motifs. By identifying homologues of E. coli genes, we also investigate the effect of gene expression level in Haemophilus influenzae and Mycoplasma genitalium. We find that while context-dependent codon biases are widespread in bacteria, few are conserved across all species considered.
Avoidance of out-of-frame stop codons does not apply to all stop codons or amino acids in E. coli, does not hold for different species, does not increase with gene expression level, and is not relaxed in Mycoplasma spp., in which the canonical stop codon, TGA, is recognized as tryptophan. Avoidance of AGG motifs shows some evolutionary
conservation and increases with gene expression level in E. coli, suggestive of the action of selection, but the cause of the bias differs between species. These results demonstrate that
strong context-dependent forces, both selective and mutational, operate on synonymous codon usage but that these differ considerably
between genomes.
Received: 6 May 1999 / Accepted: 29 October 1999 相似文献
7.
Natural selection favors certain synonymous codons which aid translation in Escherichia coli, yet codons not favored by translational selection persist. We use the frequency distributions of synonymous polymorphisms
to test three hypotheses for the existence of translationally sub-optimal codons: (1) selection is a relatively weak force,
so there is a balance between mutation, selection, and drift; (2) at some sites there is no selection on codon usage, so some
synonymous sites are unaffected by translational selection; and (3) translationally sub-optimal codons are favored by alternative
selection pressures at certain synonymous sites. We find that when all the data is considered, model 1 is supported and both
models 2 and 3 are rejected as sole explanations for the existence of translationally sub-optimal codons. However, we find
evidence in favor of both models 2 and 3 when the data is partitioned between groups of amino acids and between regions of
the genes. Thus, all three mechanisms appear to contribute to the existence of translationally sub-optimal codons in E. coli.
Received: 18 July 2000 / Accepted: 17 April 2001 相似文献
8.
杨树派间不同种的遗传密码子使用频率分析 总被引:1,自引:0,他引:1
遗传密码子的简并性特征造成了不同物种使用的密码子存在偏爱性。了解不同物种的密码子使用特点,可以为外源基因导入过程中的基因改造提供依据,从而实现外源基因的高效表达。杨树是世界上广泛栽培的重要造林树种之一,已经成为林木基因工程研究的模式植物。本研究采用高频密码子分析法,对美洲山杨P.tremuloides,毛白杨P.tomentosa,美洲黑杨P.deltoids和毛果杨P.trichocarpa 4种杨树的蛋白质编码基因序列(CDS)进行了分析,计算出了杨树同义密码子相对使用频率(RFSC),确定了4种杨树的高频率密码子,发现虽然不同种类的杨树密码子使用上有一些差别,但是偏爱密码子的差别却很小,共性的密码子占绝大多数。仅有Pro,Thr和Cys等少数几个氨基酸的偏爱密码子有差别。这种“共性”提示我们,用不同种的杨树中任何一种杨树的偏爱密码子所设计的外源基因在其他杨树中也可以使用。 相似文献
9.
Codon Usage Bias and tRNA Abundance in Drosophila 总被引:5,自引:0,他引:5
Codon usage bias of 1,117 Drosophila melanogaster genes, as well as fewer D. pseudoobscura and D. virilis genes, was examined from the perspective of relative abundance of isoaccepting tRNAs and their changes during development.
We found that each amino acid contributes about equally and highly significantly to overall codon usage bias, with the exception
of Asp which had very low contribution to overall bias. Asp was also the only amino acid that did not show a clear preference
for one of its synonymous codons. Synonymous codon usage in Drosophila was consistent with ``optimal' codons deduced from the isoaccepting tRNA availability. Interestingly, amino acids whose
major isoaccepting tRNAs change during development did not show as strong bias as those with developmentally unchanged tRNA
pools. Asp is the only amino acid for which the major isoaccepting tRNAs change between larval and adult stages. We conclude
that synonymous codon usage in Drosophila is well explained by tRNA availability and is probably influenced by developmental changes in relative abundance.
Received: 5 December 1996 / Accepted: 14 June 1997 相似文献
10.
A survey of the patterns of synonymous codon preference in the HIV env gene reveals a correlation between the codon bias and the mutability requirements of different regions of the protein. At
hypervariable regions in gp120 one finds a greater proportion of codons that tend to mutate nonsynonymously, but to a target
that is similar in hydrophobicity and volume. We argue that this strategy results from a compromise between the selective
pressure placed on the virus by the induced immune response, which favors amino acid substitutions in the complementarity
determining regions, and the negative selection against missense mutations that violate structural constraints of the env protein.
Received: 9 June 1997 / Accepted: 25 May 1998 相似文献
11.
Rajkumari Sanjukta Mohammad Samir Farooqi Naveen Sharma Anil Rai Dwijesh Chandra Mishra Dhananjaya P Singh 《Bioinformation》2012,8(22):1087-1095
Chromohalobacter salexigens, a Gammaproteobacterium belonging to the family Halomonadaceae, shows a broad salinity range for
growth. In order to reveal the factors influencing architecture of protein coding genes in C. salexigens, pattern of synonymous codon
usage bias has been investigated. Overall codon usage analysis of the microorganism revealed that C and G ending codons are
predominantly used in all the genes which are indicative of mutational bias. Multivariate statistical analysis showed that the genes
are separated along the first major explanatory axis according to their expression levels and their genomic GC content at the
synonymous third positions of the codons. Both NC plot and correspondence analysis on Relative Synonymous Codon Usage
(RSCU) indicates that the variation in codon usage among the genes may be due to mutational bias at the DNA level and natural
selection acting at the level of mRNA translation. Gene length and the hydrophobicity of the encoded protein also influence the
codon usage variation of genes to some extent. A comparison of the relative synonymous codon usage between 10% each of highly
and lowly expressed genes determines 23 optimal codons, which are statistically over represented in the former group of genes and
may provide useful information for salt-stressed gene prediction and gene-transformation. Furthermore, genes for regulatory
functions; mobile and extrachromosomal element functions; and cell envelope are observed to be highly expressed. The study
could provide insight into the gene expression response of halophilic bacteria and facilitate establishment of effective strategies to
develop salt-tolerant crops of agronomic value. 相似文献
12.
普通野生稻线粒体蛋白质编码基因密码子使用偏好性的分析 总被引:2,自引:0,他引:2
以普通野生稻(Oryza rufipogon Griff.)线粒体基因组为对象,分析其蛋白质编码基因的密码子使用特征及与亚洲栽培稻(O. sativa L.)的差异,探讨其密码子偏性形成的影响因素和进化过程。结果显示:普通野生稻线粒体基因组编码序列第1、第2和第3位碱基的GC含量依次为49.18%、42.67%和40.86%;有效密码子数(Nc)分布于45.32~61.00之间,其密码子偏性较弱; Nc值仅与GC_3呈显著相关,密码子第3位的碱基组成对密码子偏性影响较大;第1向量轴上显示9.91%的差异,其与GC3s、Nc、密码子偏好指数(CBI)和最优密码子使用频率(Fop)的相关性均达到显著水平;而GC_3和GC12的相关性未达到显著水平。因此,普通野生稻线粒体基因组密码子的使用偏性主要受自然选择压力影响而形成。本研究确定了21个普通野生稻线粒体基因组的最优密码子,大多以A或T结尾,与叶绿体密码子具有趋同进化,但是与核基因组具有不同的偏好性。同义密码子相对使用度(RSCU)、PR2偏倚分析和中性绘图分析显示,普通野生稻线粒体基因功能和其密码子使用密切相关,且线粒体密码子使用在普通野生稻、粳稻(O. sativa L. subsp. japonica Kato)和籼稻(O. sativa L. subsp.indica Kato)内具有同质性。 相似文献
13.
以普通野生稻(Oryza rufipogon Griff.)线粒体基因组为对象,分析其蛋白质编码基因的密码子使用特征及与亚洲栽培稻(O.sativa L.)的差异,探讨其密码子偏性形成的影响因素和进化过程。结果显示:普通野生稻线粒体基因组编码序列第1、第2和第3位碱基的GC含量依次为49.18%、42.67%和40.86%;有效密码子数(Nc)分布于45.32~61.00之间,其密码子偏性较弱;Nc值仅与GC3呈显著相关,密码子第3位的碱基组成对密码子偏性影响较大;第1向量轴上显示9.91%的差异,其与GC3s、Nc、密码子偏好指数(CBI)和最优密码子使用频率(Fop)的相关性均达到显著水平;而GC3和GC12的相关性未达到显著水平。因此,普通野生稻线粒体基因组密码子的使用偏性主要受自然选择压力影响而形成。本研究确定了21个普通野生稻线粒体基因组的最优密码子,大多以A或T结尾,与叶绿体密码子具有趋同进化,但是与核基因组具有不同的偏好性。同义密码子相对使用度(RSCU)、PR2偏倚分析和中性绘图分析显示,普通野生稻线粒体基因功能和其密码子使用密切相关,且线粒体密码子使用在普通野生稻、粳稻(O.sativa L.subsp.japonica Kato)和籼稻(O.sativa L.subsp.indica Kato)内具有同质性。 相似文献
14.
Richard M. Kliman 《Journal of molecular evolution》1999,49(3):343-351
Evidence from a variety of sources indicates that selection has influenced synonymous codon usage in Drosophila. It has generally been difficult, however, to distinguish selection that acted in the distant past from ongoing selection.
However, under a neutral model, polymorphisms usually reflect more recent mutations than fixed differences between species
and may, therefore, be useful for inferring recent selection. If the ancestral state is preferred, selection should shift
the frequency distribution of derived states/site toward lower values; if the ancestral is unpreferred, selection should increase
the number of derived states/site. Polymorphisms were classified as ancestrally preferred or unpreferred for several genes
of D. simulans and D. melanogaster. A computer simulation of coalescence was employed to derive the expected frequency distributions of derived states/site under
various modifications of the Wright–Fisher neutral model, and distributions of test statistics (t and Mann–Whitney U) were derived by appropriate sampling. One-tailed tests were applied to transformed frequency data to assess whether the
two frequency distributions deviated from neutral expectations in the direction predicted by selection on codon usage. Several
genes from D. simulans appear to be subject to recent selection on synonymous codons, including one gene with low codon bias, esterase-6. Selection may also be acting in D. melanogaster.
Received: 15 April 1998 / Accepted: 13 May 1999 相似文献
15.
To understand the synonymous codon usage pattern in mitochondrial genome of Antheraea assamensis, we analyzed the 13 mitochondrial protein‐coding genes of this species using a bioinformatic approach as no work was reported yet. The nucleotide composition analysis suggested that the percentages of A, T, G,and C were 33.73, 46.39, 9.7 and 10.17, respectively and the overall GC content was 19.86, that is, lower than 50% and the genes were AT rich. The mean effective number of codons of mitochondrial protein‐coding genes was 36.30 and it indicated low codon usage bias (CUB). Relative synonymous codon usage analysis suggested overrepresented and underrepresented codons in each gene and the pattern of codon usage was different among genes. Neutrality plot analysis revealed a narrow range of distribution for GC content at the third codon position and some points were diagonally distributed, suggesting both mutation pressure and natural selection influenced the CUB. 相似文献
16.
Synonymous and nonsynonymous rate variation in nuclear genes of mammals 总被引:34,自引:6,他引:28
A maximum likelihood approach was used to estimate the synonymous and nonsynonymous substitution rates in 48 nuclear genes
from primates, artiodactyls, and rodents. A codon-substitution model was assumed, which accounts for the genetic code structure,
transition/transversion bias, and base frequency biases at codon positions. Likelihood ratio tests were applied to test the
constancy of nonsynonymous to synonymous rate ratios among branches (evolutionary lineages). It is found that at 22 of the
48 nuclear loci examined, the nonsynonymous/synonymous rate ratio varies significantly across branches of the tree. The result
provides strong evidence against a strictly neutral model of molecular evolution. Our likelihood estimates of synonymous and
nonsynonymous rates differ considerably from previous results obtained from approximate pairwise sequence comparisons. The
differences between the methods are explored by detailed analyses of data from several genes. Transition/transversion rate
bias and codon frequency biases are found to have significant effects on the estimation of synonymous and nonsynonymous rates,
and approximate methods do not adequately account for those factors. The likelihood approach is preferable, even for pairwise
sequence comparison, because more-realistic models about the mutation and substitution processes can be incorporated in the
analysis.
Received: 17 May 1997 / Accepted: 28 September 1997 相似文献
17.
Synonymous Codon Choices in the Extremely GC-Poor Genome of Plasmodium falciparum: Compositional Constraints and Translational Selection 总被引:7,自引:0,他引:7
Héctor Musto Héctor Romero Alejandro Zavala Kamel Jabbari Giorgio Bernardi 《Journal of molecular evolution》1999,49(1):27-35
We have analyzed the patterns of synonymous codon preferences of the nuclear genes of Plasmodium falciparum, a unicellular parasite characterized by an extremely GC-poor genome. When all genes are considered, codon usage is strongly
biased toward A and T in third codon positions, as expected, but multivariate statistical analysis detects a major trend among
genes. At one end genes display codon choices determined mainly by the extreme genome composition of this parasite, and very
probably their expression level is low. At the other end a few genes exhibit an increased relative usage of a particular subset
of codons, many of which are C-ending. Since the majority of these few genes is putatively highly expressed, we postulate
that the increased C-ending codons are translationally optimal. In conclusion, while codon usage of the majority of P. falciparum genes is determined mainly by compositional constraints, a small number of genes exhibit translational selection.
Received: 10 November 1998 / Accepted: 28 January 1999 相似文献
18.
目前,有关同义密码子使用偏性对蛋白质折叠的影响研究中,样本蛋白均来源于不同的物种。考虑到同义密码子使用偏性的物种差异性,选取枯草杆菌的核蛋白为研究对象。首先,将每条核蛋白按二级结构截取为α螺旋片段、β折叠片段和无规卷曲(α-β混合)片段,并计算其蛋白质折叠速率。然后,整理每个片段相应的核酸序列信息,计算其同义密码子使用度。在此基础上,分析枯草芽孢杆菌核蛋白的同义密码子使用偏性与蛋白质折叠速率的相关性。发现对于不同二级结构的肽链片段,都有部分密码子的使用偏性与其对应的肽链折叠速率显著相关。进一步分析发现,与肽链片段折叠速率显著相关的密码子绝大部分为枯草杆菌全序列或核蛋白序列的每一组同义密码子中使用度最高的密码子。结果表明,在蛋白质的折叠过程中,枯草芽孢杆菌的同义密码子使用偏性起着重要作用。 相似文献
19.
Codon bias is the non-random use of synonymous codons, a phenomenon that has been observed in species as diverse as bacteria, plants and mammals. The preferential use of particular synonymous codons may reflect neutral mechanisms (e.g. mutational bias, G|C-biased gene conversion, genetic drift) and/or selection for mRNA stability, translational efficiency and accuracy. The extent to which these different factors influence codon usage is unknown, so we dissected the contribution of mutational bias and selection towards codon bias in genes from 15 eudicots, 4 monocots and 2 mosses. We analysed the frequency of mononucleotides, dinucleotides and trinucleotides and investigated whether the compositional genomic background could account for the observed codon usage profiles. Neutral forces such as mutational pressure and G|C-biased gene conversion appeared to underlie most of the observed codon bias, although there was also evidence for the selection of optimal translational efficiency and mRNA folding. Our data confirmed the compositional differences between monocots and dicots, with the former featuring in general a lower background compositional bias but a higher overall codon bias. 相似文献
20.
Rates of synonymous and nonsynonymous nucleotide substitutions and codon usage bias (ENC) were estimated for a number of
nuclear and chloroplast genes in a sample of centric and pennate diatoms. The results suggest that DNA evolution has taken
place, on an average, at a slower rate in the chloroplast genes than in the nuclear genes: a rate variation pattern similar
to that observed in land plants. Synonymous substitution rates in the chloroplast genes show a negative association with the
degree of codon usage bias, suggesting that genes with a higher degree of codon usage bias have evolved at a slower rate.
While this relationship has been shown in both prokaryotes and multicellular eukaryotes, it has not been demonstrated before
in diatoms.
Received: 3 June 1998 / Accepted: 11 August 1998 相似文献