Codon Pair Utilization Biases Influence Translational Elongation Step Times
The universal genetic code is made up of several codons or triplet bases. are no tRNAs with anticodons complementary to the STOP codons. We discuss the way changes in the bases in the anticodon influence both the speed .. Thus, we expect to see a consistent relationship between preferred Dick Morton, and Herb Schellhorn for helpful advice and criticism. pairs between the codons and the tRNA anticodons are .. dehydrogenase ( G3PDH) genes in relationship to anticodon sequences in the major .. Templeton for their advice concerning this manuscript and Jon. Gallant and.
Translational selection causes a significant bias in codon frequencies in highly expressed genes in most bacteria. By comparing codon frequencies in high and low-expression genes, we determine which codons are preferred for each amino acid in a large sample of bacterial genomes.
We relate this to the number of copies of each tRNA gene in each genome. In two-codon families, preferred codons have Watson—Crick pairs GC and AU between the third codon base and the wobble base of the anticodon rather than GU pairs.
This suggests that these combinations are more rapidly recognized by the ribosome. In contrast, in four-codon families, preferred codons do not correspond to Watson—Crick rules. In some cases, a wobble-U tRNA can pair with all four codons. In these cases, A and U codons are preferred over G and C. This indicates that the nonstandard UU combination appears to be translated surprisingly well.
Differences in modified bases at the wobble position of the anticodon appear to be responsible for the differences in behavior of tRNAs in two- and four-codon families.
We discuss the way changes in the bases in the anticodon influence both the speed and the accuracy of translation. The number of tRNA gene copies and the strength of translational selection correlate with the growth rate of the organism, as we would expect if the primary cause of translational selection in bacteria is the requirement to optimize the speed of protein production.
Translation (mRNA to protein)
In particular, selection acts to increase the frequency of preferred codons in high-expression genes, such as ribosomal proteins Sharp and Li It is also well known that preferred codons tend to correspond to the transfer RNAs tRNAs that have the highest concentrations in cells Ikemura It is presumed that high tRNA concentration leads to rapid translation and that this is an advantage to organisms that require a rapid rate of protein production.
The total number of tRNA gene copies in bacterial genomes varies from fewer than 30 to more than due to the presence of duplicate copies of some tRNA genes in some genomes.
In cases where tRNA concentrations have been measured Kanaya et al. Rocha showed that the total number of tRNA gene copies in bacterial genomes correlates with the doubling rate of the cells. Bacteria that require a high growth rate require duplicate tRNAs. Translational selection also influences the relative frequencies of codons that are translated by the same tRNA. In particular, amino acids with two-codon families ending in U and C have a single type of tRNA that has a G at the wobble position.
This G pairs with both bases at the third codon position see fig. This preference cannot be explained by variation of tRNA concentration and gene copy number. We have demonstrated that an over-represented codon pair is translated slower than an under-represented codon pair, and that the more over-represented a codon pair is, the slower it is translated. These effects of codon pair bias on translation are consistent with the facts that codon pair biases in E. In addition to supporting the correlation between codon pair bias and translational efficiency, this observation also shows that translational efficiency is more closely related to codon context codon pair bias than it is to the utilization frequency of individual codons.
If the differing translation rates were due primarily to the frequency of usage of one or the other of these codons then the translation rates in both orientations would be expected to be the same. The data presented in Table 1 also show that two codon pairs with nearly equal codon pair bias values, but encoding different amino acid pairs and differing at all six nucleotide positions, can exhibit the same translational efficiency compare strains IH78 and IH This observation suggests a close relationship between codon pair values and translational efficiency.
However, this close relationship might not be observed in every case.Codon and Anticodon (practice problem)
For example, it is known that identical codons located at different positions in an mRNA can be read by different isoacceptor tRNAs Holmes et al.
Therefore, if translational efficiency is the consequence of the compatability of adjacent tRNA molecules on a translating ribosome, then the translational step time across a given codon pair could differ depending on the identity of the tRNA molecules decoding these codons. In this case, other factors that affect isoacceptor tRNA selection, such as III-I dinucleotide biases and codon-anticodon stacking energies, could also affect translational efficiency.
These sorts of effects on the results presented in Table 1 cannot be excluded. To confirm the conclusions drawn from the results of the translation initiation assay, we employed an independent trp attenuator-based assay to examine the translational efficiency of the same highly over-represented and under-represented codon pairs. With this assay we demonstrated that the highly under-represented Leu-Thr codon pair ACC CUG, CHISQ 3 that severely inhibits translation initiation also restricts translation of the polypeptide coding sequence in the trp leader-attenuator region and causes increased transcription through the trp attenuator.
If this is so, then it is reasonable to assume that the use of one codon next to another has co-evolved with the structure and abundance of tRNA isoacceptors in order to control the rates of translational step times without imposing additional constraints on amino acid sequences or protein structures.
This hypothesis offers a simple explanation for the large, seemingly excessive, number of tRNA isoacceptor molecules found in all living cells.
It implies that, for any given amino acid sequence, appropriately biased codon pairs can be employed to set the translational step times for the addition of amino acids to the growing polypeptide chain. In this manner, translational pauses important for the folding and other functions of nascent polypeptide chains can be incorporated into the DNA coding sequence of a gene.
However, since the relative translational efficiencies of only a small number of codon pairs have been studied, it is not yet possible to ascertain how consistent the relationship between translational step times and codon pair bias values will be. As more codon pairs are examined, it will be interesting to determine if it is possible to use these values in a way that will be predictive of relative translational step times for the identification of translational pause sites.
In summary, we have employed two independent assays to demonstrate a close relationship between the translational efficiency of a codon pair and its degree of bias in protein coding sequences of E.
Difference Between Anticodon and Codon | Difference Between | Anticodon vs Codon
We have demonstrated that at least some codon pairs that are observed in protein coding sequences more frequently than predicted by the frequency of the individual codons in that pair are translated slower than codon pairs that are found less frequently than expected. Additionally, we have demonstrated a general relationship between the utilization bias of a codon pair and its translational bias; the more over-represented these codon pairs are the slower they are translated, and the more under-represented they are the faster they are translated.
This means that wobble decoding modulates the efficiency of elongation, a primary catalytic function of the ribosome. The inhibition of expression reported here is clearly caused by translation of the CGA codon, and not by poly-arginine, since the expression effect is codon-dependent, is suppressible by the anticodon-mutated tRNAArg UCGand does not require long stretches of arginine.
Second, although the loss of expression caused by defects in decoding CGA codons is not mediated by mRNA degradation, CGA codons do result in formation of a novel RNA, most likely due to endonucleolytic cleavage near a stalled ribosome.
Control of translation efficiency in yeast by codon–anticodon interactions
This means that translation of sense codons can induce a strong and efficient halt to translation. Third, adjacent CGA codons are far more potent inhibitors of expression than separated CGA codons, a phenomenon most easily ascribed to interactions within the ribosome.
Thus, profound differences in translation efficiency can stem directly from decoding interactions in the ribosome.
Observations from our work and others provide two clues to the mechanism by which CGA decoding impairs translation efficiency.
Second, CGA codons are likely to exert their effects in two successive steps during translation, since adjacent CGA codons have a synergistic effect on expression. Zaher and Green recently identified a quality control pathway in E. A similar pathway in yeast that probes the codon—anticodon interaction in the P site would account for the increased potency of adjacent CGA codons.
Many translation defects are closely coupled to mRNA degradation.