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Codon usage and gene expression.   总被引:36,自引:16,他引:20       下载免费PDF全文
L Holm 《Nucleic acids research》1986,14(7):3075-3087
The hypothesis that codon usage regulates gene expression at the level of translation is tested. Codon usage of Escherichia coli and phage lambda is compared by correspondence analysis, and the basis of this hypothesis is examined by connecting codon and tRNA distributions to polypeptide elongation kinetics. Both approaches indicate that if codon usage was random tRNA limitation would only affect the rarest tRNA species. General discrimination against their cognate codons indicates that polypeptide elongation rates are maintained constant. Thus, differences in expression of E. coli genes are not a consequence of their variable codon usage. The preference of codons recognized by the most abundant tRNAs in E. coli genes encoding abundant proteins is explained by a constraint on the cost of proof-reading.  相似文献   

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Codon usage data of bacteriophage T4 genes were compiled and synonymous codon preferences were investigated in comparison with tRNA availabilities in an infected cell. Since the genome of T4 is highly AT rich and its codon usage pattern is significantly different from that of its host Escherichia coli, certain codons of T4 genes need to be translated by appropriate host transfer RNAs present in minor amounts. To avoid this predicament, T4 phage seems to direct the synthesis of its own tRNA molecules and these phage tRNAs are suggested to supplement the host tRNA population with isoacceptors that are normally present in minor amounts. A positive correlation was found in that the frequency of E. coli optimal codons in T4 genes increases as the number of protein monomers per phage particle increases. A negative correlation was also found between the number of protein monomers per phage and the frequency of "T4 optimal codons", which are defined as those codons that are efficiently recognized by T4 tRNAs. From these observations it was proposed that tRNAs from the host are predominantly used for translation of highly expressed T4 genes while tRNAs from T4 tend to be used for translation of weakly expressed T4 genes. This distinctive tRNA-usage in T4 may be an optimization of translational efficiency, and an adjustment of T4-encoded tRNAs to the synonymous codon preferences, which are largely influenced by the high genomic AT-content, would have occurred during evolution.  相似文献   

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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   

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The relative quantities of 26 known transfer RNAs of Escherichia coli have been measured previously (Ikemura, 1981). Based on this relative abundance, the usage of cognate codons in E. coli genes as well as in transposon and coliphage genes was examined. A strong positive correlation between tRNA content and the occurrence of respective codons was found for most E. coli genes that had been sequenced, although the correlation was less significant for transposon and phage genes. The dependence of the usage of isoaccepting tRNA, in E. coli genes encoding abundant proteins, on tRNA content was especially noticeable and was greater than that expected from the proportional relationship between the two variables, i.e. these genes selectively use codons corresponding to major tRNAs but almost completely avoid using codons of minor tRNAs. Therefore, codon choice in E. coli genes was considered to be largely constrained by tRNA availability and possibly by translational efficiency. Based on the content of isoaccepting tRNA and the nature of codon-anticodon interaction, it was then possible to predict for most amino acids the order of preference among synonymous codons. The synonymous codon predicted in this way to be the most preferred codon was thought to be optimized for the E. coli translational system and designated as the “Optimal codon”. E. coli genes encoding abundant protein species use the optimal codons selectively, and other E. coli genes, such as amino acid synthesizing genes, use optimal and “non-optimal” codons to a roughly equal degree. The finding that the frequency of usage of optimal codons is closely correlated with the production levels of individual genes was discussed from an evolutionary viewpoint.  相似文献   

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Insects, the most biodiverse taxonomic group, have high AT content in their mitochondrial genomes. Although codon usage tends to be AT-rich, base composition and codon usage of mitochondrial genomes may vary among taxa. Thus, we compare base composition and codon usage patterns of 49 insect mitochondrial genomes. For protein coding genes, AT content is as high as 80% in the Hymenoptera and Lepidoptera and as low as 72% in the Orthopotera. The AT content is high at positions 1 and 3, but A content is low at position 2. A close correlation occurs between codon usage and tRNA abundance in nuclear genomes. Optimal codons can pair well with the antr codons of the most abundant tRNAs. One tRNA gene translates a synonymous codon family in vertebrate mitochondrial genomes and these tRNA anticodons can pair with optimal codons. However, optimal codons cannot pair with anticodons in mtDNA ofCochiiomyia hominivorax (Dipteral: CaLliphoridae). Ten optimal codons cannot pair with tRNA anticodons in all 49 insect mitochondrial genomes; non-optimal codon-anticodon usage is common and codon usage is not influenced by tRNA abundance.  相似文献   

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Elongation in protein translation is strongly dependent on the availability of mature transfer RNAs (tRNAs). The relative concentrations of the tRNA isoacceptors determine the translation efficiency in unicellular organisms. However, the degree of correspondence of codons and the relevant tRNA isoacceptors serves as an estimator for translation efficiency in all organisms. In this study, we focus on the translational capacity of the human proteome. We show that the correspondence between the codon usage and tRNAs can be improved by combining experimental measurements with the genomic copy number of isoacceptor groups. We show that there are technologies of tRNA measurements that are useful for our analysis. However, fragments of tRNAs do not agree with translational capacity. It was shown that there is a significant increase in the absolute levels of tRNA genes in cancerous cells in comparison to healthy cells. However, we find that the relative composition of tRNA isoacceptors in healthy, cancerous, or transformed cells remains almost identical. This result may indicate that maintaining the relative tRNA composition in cancerous cells is advantageous via its stabilizing of the effectiveness of translation.  相似文献   

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The mitochondrial genome of Chlamydomonas reinhardtii only encodes three expressed tRNA genes, thus most mitochondrial tRNAs are likely imported. The sharing of tRNAs between chloroplasts and mitochondria has been speculated in this organism. We first demonstrate that no plastidial tRNA is present in mitochondria and that the mitochondrial translation mainly relies on the import of nucleus-encoded tRNA species. Then, using northern analysis, we show that the extent of mitochondrial localization for the 49 tRNA isoacceptor families encoded by the C. reinhardtii nuclear genome is highly variable. Until now the reasons for such variability were unknown. By comparing cytosolic and mitochondrial codon usage with the sub-cellular distribution of tRNAs, we provide unprecedented evidence that the steady-state level of a mitochondrial tRNA is linked not only to the frequency of the cognate codon in mitochondria but also to its frequency in the cytosol, then allowing optimal mitochondrial translation.  相似文献   

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Aminoacylated (charged) transfer RNA isoacceptors read different messenger RNA codons for the same amino acid. The concentration of an isoacceptor and its charged fraction are principal determinants of the translation rate of its codons. A recent theoretical model predicts that amino-acid starvation results in 'selective charging' where the charging levels of some tRNA isoacceptors will be low and those of others will remain high. Here, we developed a microarray for the analysis of charged fractions of tRNAs and measured charging for all Escherichia coli tRNAs before and during leucine, threonine or arginine starvation. Before starvation, most tRNAs were fully charged. During starvation, the isoacceptors in the leucine, threonine or arginine families showed selective charging when cells were starved for their cognate amino acid, directly confirming the theoretical prediction. Codons read by isoacceptors that retain high charging can be used for efficient translation of genes that are essential during amino-acid starvation. Selective charging can explain anomalous patterns of codon usage in the genes for different families of proteins.  相似文献   

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Peptide elongation proceeds by tRNA anticodons recognizing mRNA codons coding for the tRNA's cognate amino acid. Putatively, tRNAs possess three anticodons because tRNA side and anticodon-arms form similar stem-loop structures. Two lines of evidence indicate that mammal mitochondrial tRNA sidearms function as anticodons: numbers of TΨC-arm ‘anticodons’ matching specific cognates coevolve with that cognate's usage in mitochondrial genomes; and predicted ‘tetragene’ numbers, genes coded by quadruplet codons (tetracodons), coevolve with numbers of expanded anticodons in D-arms, as previously observed between tetragenes and antisense tRNA expanded anticodons. Sidearms with long stems and high GC contents contribute most to tRNA sidearm-tetragene coevolution. Results are compatible with two hypothetical mechanisms for translation by side-arms: crossovers exchange anticodon- and side-arms; tRNA sidearms are excised, aminoacylated and function as isolated stem-loop hairpins (more probable for long, respectively stable branches). Isolated sidearms would resemble recently described armless ‘minimal’ tRNAs. Isolated hairpins might most parsimoniously explain observed patterns. tRNA genes templating for three, rather than one functional tRNA, compress minimal genome size. Results suggest fused tRNA halves form(ed) modern tRNAs, isolated tRNA subparts occasionally translate proteins. Results confirm translational activity by antisense tRNAs, whose anticodons also coevolve with codon usages. Accounting for antisense anticodons improves results for sidearm anticodons.  相似文献   

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Over 450 transfer RNA (tRNA) genes have been annotated in the human genome. Reliable quantitation of tRNA levels in human samples using microarray methods presents a technical challenge. We have developed a microarray method to quantify tRNAs based on a fluorescent dye-labeling technique. The first-generation tRNA microarray consists of 42 probes for nuclear encoded tRNAs and 21 probes for mitochondrial encoded tRNAs. These probes cover tRNAs for all 20 amino acids and 11 isoacceptor families. Using this array, we report that the amounts of tRNA within the total cellular RNA vary widely among eight different human tissues. The brain expresses higher overall levels of nuclear encoded tRNAs than every tissue examined but one and higher levels of mitochondrial encoded tRNAs than every tissue examined. We found tissue-specific differences in the expression of individual tRNA species, and tRNAs decoding amino acids with similar chemical properties exhibited coordinated expression in distinct tissue types. Relative tRNA abundance exhibits a statistically significant correlation to the codon usage of a collection of highly expressed, tissue-specific genes in a subset of tissues or tRNA isoacceptors. Our findings demonstrate the existence of tissue-specific expression of tRNA species that strongly implicates a role for tRNA heterogeneity in regulating translation and possibly additional processes in vertebrate organisms.  相似文献   

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The typical number of tRNA genes in bacterial genomes is around 50, but this number varies from under 30 to over 120. We argue that tRNA gene copy numbers evolve in response to translational selection. In rapidly multiplying organisms, the time spent in translation is a limiting factor in cell division; hence, it pays to duplicate tRNA genes, thereby increasing the concentration of tRNA molecules in the cell and speeding up translation. In slowly multiplying organisms, translation time is not a limiting factor, so the overall translational cost is minimized by reducing the tRNAs to only one copy of each required gene. Translational selection also causes a preference for codons that are most rapidly translated by the current tRNAs; hence, codon usage and tRNA gene content will coevolve to a state where each is adapted to the other. We show that there is often more than one stable coevolved state. This explains why different combinations of tRNAs and codon bias can exist for different amino acids in the same organism. We analyze a set of 80 complete bacterial genomes and show that the theory predicts many of the trends that are seen in these data.  相似文献   

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In all domains of life, initiator tRNA functions exclusively at the first step of protein synthesis while elongator tRNAs extend the polypeptide chain. Unique features of initiator tRNA enable it to preferentially bind the ribosomal P site and initiate translation. Recently, we showed that the abundance of initiator tRNA also contributes to its specialized role. This motivates the question, can a cell also use elongator tRNA to initiate translation under certain conditions? To address this, we introduced non-AUG initiation codons CCC (Pro), GAG (Glu), GGU (Gly), UCU (Ser), UGU (Cys), ACG (Thr), AAU (Asn), and AGA (Arg) into the uracil DNA glycosylase gene (ung) used as a reporter gene. Enzyme assays from log-phase cells revealed initiation from non-AUG codons when intracellular initiator tRNA levels were reduced. The activity increased significantly in stationary phase. Further increases in initiation from non-AUG codons occurred in both growth phases upon introduction of plasmid-borne genes of cognate elongator tRNAs. Since purine-rich Shine-Dalgarno sequences occur frequently on mRNAs (in places other than the canonical AUG codon initiation contexts), initiation with elongator tRNAs from the alternate contexts may generate proteome diversity under stress without compromising genomic integrity. Thus, by changing the relative amounts of initiator and elongator tRNAs within the cell, we have blurred the distinction between the two classes of tRNAs thought to be frozen through years of evolution.  相似文献   

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Codon usage data has been compiled for 110 yeast genes. Cluster analysis on relative synonymous codon usage revealed two distinct groups of genes. One group corresponds to highly expressed genes, and has much more extreme synonymous codon preference. The pattern of codon usage observed is consistent with that expected if a need to match abundant tRNAs, and intermediacy of tRNA-mRNA interaction energies are important selective constraints. Thus codon usage in the highly expressed group shows a higher correlation with tRNA abundance, a greater degree of third base pyrimidine bias, and a lesser tendency to the A+T richness which is characteristic of the yeast genome. The cluster analysis can be used to predict the likely level of gene expression of any gene, and identifies the pattern of codon usage likely to yield optimal gene expression in yeast.  相似文献   

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Translational stop codon readthrough provides a regulatory mechanism of gene expression that is extensively utilised by positive-sense ssRNA viruses. The misreading of termination codons is achieved by a variety of naturally occurring suppressor tRNAs whose structure and function is the subject of this survey. All of the nonsense suppressors characterised to date (with the exception of selenocysteine tRNA) are normal cellular tRNAs that are primarily needed for reading their cognate sense codons. As a consequence, recognition of stop codons by natural suppressor tRNAs necessitates unconventional base pairings in anticodon–codon interactions. A number of intrinsic features of the suppressor tRNA contributes to the ability to read non-cognate codons. Apart from anticodon–codon affinity, the extent of base modifications within or 3′ of the anticodon may up- or down-regulate the efficiency of suppression. In order to out-compete the polypeptide chain release factor an absolute prerequisite for the action of natural suppressor tRNAs is a suitable nucleotide context, preferentially at the 3′ side of the suppressed stop codon. Three major types of viral readthrough sites, based on similar sequences neighbouring the leaky stop codon, can be defined. It is discussed that not only RNA viruses, but also the eukaryotic host organism might gain some profit from cellular suppressor tRNAs.  相似文献   

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