Preferred and avoided codon pairs in three domains of life

Codon context can influence translational elongation rates.

“It is suggested that codon context biases are associated with translational efficiency, since codon context influences translational elongation rates [1].”

• cites [1] Irwin B, Heck JD, Hatfield GW: Codon pair utilization biases influence translational elongation step times. J Biol Chem. 1995, 270 (39): 22801-22806. 10.1074/jbc.270.39.22801. sourceSupported

Codon context is more strongly related to translational efficiency than single codon usage.

“Moreover, experimental results support the observation that codon context is more strongly related to translational efficiency than single codon usage [1].”

• cites [1] Irwin B, Heck JD, Hatfield GW: Codon pair utilization biases influence translational elongation step times. J Biol Chem. 1995, 270 (39): 22801-22806. 10.1074/jbc.270.39.22801. sourceSupported

In five gamma proteobacteria, Bacillus subtilis and two yeasts, A-site codons decoded by the same tRNA have similar patterns of P-site codon pairing preference.

“It has been shown that in five gamma proteobacteria, Bacillus subtilis and two yeasts, the A-site codons decoded by the same tRNA have similar patterns of P-site codon pairing preference [16].”

• cites [16] Buchan JR, Aucott LS, Stansfield I: tRNA properties help shape codon pair preferences in open reading frames. Nucleic Acids Res. 2006, 34 (3): 1015-1027. 10.1093/nar/gkj488. sourceSupported

Mononucleotide repeats, especially poly(A) and poly(U) tracts, cause transcriptional and translational frameshifting.

“Mononucleotide repeats, especially poly(A) and poly(U) tracts, are also known to cause transcriptional and translational frameshifting [8-10].”

• cites [8] Baranov PV, Hammer AW, Zhou J, Gesteland RF, Atkins JF: Transcriptional slippage in bacteria: distribution in sequenced genomes and utilization in IS element gene expression. Genome Biol. 2005, 6 (3): R25-10.1186/gb-2005-6-3-r25. sourcePartly supported

  The Background describes transcriptional slippage at a run of nine As, producing mRNAs with different reading frames. It also describes ribosomal frameshifting in E. coli, but does not establish that poly(A) or poly(U) tracts cause that translational frameshifting. The Discussion likewise supports transcriptional slippage on A and T runs, not both mechanisms. (LLM, conf=0.84)

  Experimental — accuracy not yet measured
• cites [9] Wagner LA, Weiss RB, Driscoll R, Dunn DS, Gesteland RF: Transcriptional slippage occurs during elongation at runs of adenine or thymine in Escherichia coli. Nucleic Acids Res. 1990, 18 (12): 3529-3535. 10.1093/nar/18.12.3529. sourcePartly supported

  The title (p. 3529) identifies transcriptional slippage at runs of adenine or thymine in E. coli, supporting the transcriptional part of the claim. The available passage does not address translational frameshifting or establish the claim for mononucleotide repeats generally. (LLM, conf=0.82)

  Experimental — accuracy not yet measured
• cites [10] Gurvich OL, Baranov PV, Zhou J, Hammer AW, Gesteland RF, Atkins JF: Sequences that direct significant levels of frameshifting are frequent in coding regions of Escherichia coli. Embo J. 2003, 22 (21): 5941-5950. 10.1093/emboj/cdg561. sourcePartly supported

  The A_AAA_AAG section reports ribosomal frameshifting at an A-rich sequence, and the CCC_UGA section reports frameshifting during translation at UUU_U/C. These support the translational part of the claim, but the paper does not establish that mononucleotide repeats cause transcriptional frameshifting. (LLM, conf=0.86)

  Experimental — accuracy not yet measured

With one exception (codon pair UUUUUU and pattern UnnnnU), all sub-patterns contained a fixed nucleotide in the last position of the P-site codon in the codon pair.

“Still, with one exception (codon pair UUUUUU and pattern UnnnnU), all sub-patterns contained a fixed nucleotide in the last position of the P-site codon in the codon pair.”

All different preferred sub-patterns that caused codon pair preferences contained a fixed last nucleotide of the P-site codon in the pair.

“As in the conserved avoided codon pairs, all the different preferred sub-patterns that caused codon pair preferences contained a fixed last nucleotide of the P-site codon in the pair.”

Some phylogenetic classes were similarly clustered in both trees, e.g. bacilli, gamma-proteobacteria and alpha-proteobacteria.

“Some were similarly clustered in both trees, e.g. bacilli, gamma-proteobacteria and alpha-proteobacteria.”

The third type, type 3A, contained the pattern nnCGCn.

“The third type, type 3A contained the pattern nnCGCn.”

UUCGCA contains several clearly avoided sub-patterns (UUCGnn, nnCGCn, nnCnnA).

“It is interesting to note that this codon pair contains several clearly avoided sub-patterns (UUCGnn, nnCGCn, nnCnnA).”

All major preferred types were more strongly over-represented in ORFeomes than in genomes.

“All the major types were more strongly over-represented in ORFeomes than in genomes, again indicating that the common preference of codon pairs that we detected is mainly influenced by translational mechanisms.”

Four major preferred types can be described: nnGCnn, nnCAnn, nnUUnn and nnUnCn.

“Four major preferred types can be described: nnGCnn, nnCAnn, nnUUnn and nnUnCn (Table 4).”

Genome size has a statistical effect on the number of biased codon pairs detected.

“The results show that genome size indeed has a statistical effect on the number of biased codon pairs detected.”

Codon usage gives stronger similarity between different organisms than codon pair usage.

“Comparing the RSCU and RDCU trees, we observed that the branch lengths were shorter in the RSCU tree (Figure 6A) than in the RDCU (codons 1–2) tree (Figure 6B), showing that codon usage gives stronger similarity between different organisms than codon pair usage.”

• Also stated in: § Discussion · plain

  “However, the comparison of RSCU and RDCU correlations showed that overall codon pair usage is less conserved than single codon usage (Figure 5).”

Some combinations of neighboring codons are similarly avoided or preferred in many different organisms - bacteria, archaea and eukaryotes.

“We found that some combinations of neighboring codons are similarly avoided or preferred in many different organisms – bacteria, archaea and eukaryotes.”

95.7% of avoided nnUAnn type patterns contain out-frame UAA or UAG triplets on the sense and/or antisense strand.

“We discovered that 95.7% of avoided nnUAnn type patterns contain out-frame UAA or UAG triplets on the sense and/or antisense strand.”

• Also stated in: § Under-represented codon pairs can be divided into 9 major types · plain

  “Including the antisense strand, almost all (67/70, 95.7%) of the nnUAnn type patterns contained UAA or UAG in -1 frame, although nnUAnn could code for other hexamers containing UAU and UAC in 25% of cases.”

Genome size was not the reason why B. aphidicola and C. blochmannia have low numbers of biased codon pairs.

“However, the same figure also demonstrates that genome size was not the reason why B. aphidicola and C. blochmannia have low numbers of biased codon pairs.”

The genomes of B. aphidicola and C. blochmannia were among the smallest in the study.

“The genomes of B. aphidicola and C. blochmannia were also among the smallest in our study.”

The avoided codon pairs can be divided into 9 major groups.

“The avoided codon pairs could be divided into 9 major groups (Table 2, [additional file 4]).”

The universal effect of nnUAnn avoidance is clearly visible in the human genome, where 77.1% of nnUAnn type pairs were more strongly avoided in the human ORFeome than in the genome.

“This universal effect is clearly visible in the human genome, where the nnUAnn type codon pairs were also less frequent than expected (77.1% of nnUAnn type pairs were more strongly avoided in the human ORFeome than in the genome).”

The most frequently preferred codon pairs contain the patterns nnGCnn, nnCAnn or nnUnCn.

“The most frequently preferred codon pairs contain the patterns nnGCnn, nnCAnn or nnUnCn.”

The fraction of biased codon pairs leveled off after genome reduction.

“The fraction of biased codon pairs leveled off after genome reduction (Figure 4B).”

The most frequently avoided codon pairs contain the patterns nnUAnn, nnGGnn, nnGnnC, nnCGCn, GUCCnn, CUCCnn, nnCnnA or UUCGnn.

“The most frequently avoided codon pairs contain the patterns nnUAnn, nnGGnn, nnGnnC, nnCGCn, GUCCnn, CUCCnn, nnCnnA or UUCGnn.”

The most frequently avoided type of codon pair is nnUAnn.

“The most frequently avoided type of codon pair was nnUAnn.”

• Also stated in: § Under-represented codon pairs can be divided into 9 major types · plain

  “The most abundant types of under-represented pairs were nnUAnn (Type 1A).”

Conserved biased codon pairs can be divided into subtypes on the basis of nucleotide patterns that influence the bias.

“Such biased codon pairs could be divided into subtypes on the basis of the nucleotide patterns that influence the bias.”

The most avoided and the most preferred codon pairs are uniformly distributed across all three domains of life.

“It can be seen that the most avoided and the most preferred codon pairs are uniformly distributed across all three domains of life.”

The conserved avoidances and preferences of codon pairs observed are not the result of dipeptide biases.

“The conserved avoidances and preferences of codon pairs observed are not the result of dipeptide biases since the effect of dipeptides was removed.”

UUCGCA was similarly under-represented on both the ORFeome and genome levels.

“The observed/expected ratios of this pair in the ORFeome and genome indicated that UUCGCA was similarly under-represented on both the ORFeome and genome levels (Table 1).”

The most conserved avoided codon pair was UUCGCA (type 6A, UUCGnn), which was under-represented in 86% of the organisms studied.

“The most conserved avoided codon pair was UUCGCA (type 6A, UUCGnn), which was under-represented in 86% of the organisms studied.”

The correlation of RSCU values was generally higher than the correlation of RDCU values.

“We observed that the correlation of RSCU values was generally higher than the correlation of RDCU values (Figure 5).”

Five organisms showed significant bias in fewer than five of the top 20 codon pairs.

“Interestingly, five organisms showed significant bias in fewer than five of the top 20 codon pairs (Figures 2 and 3).”

83% (58/70) of nnUAnn type patterns contained out-frame UAA and UAG triplets on the antisense strand.

“Interestingly, 83% (58/70) of the nnUAnn type patterns contained out-frame UAA and UAG triplets on the antisense strand.”

207 codon pairs were avoided in the ORFs of more than half the organisms studied.

“We identified 207 codon pairs that were avoided in the ORFs of more than half the organisms studied (Table 1, [additional file 1]).”

Much of the dataset could be divided into subtypes on the basis of nucleotide patterns influencing the bias of codon pairs.

“Much of the dataset could be divided into subtypes on the basis of nucleotide patterns influencing the bias of codon pairs.”

Buchnera aphidicola and Candidatus blochmannia pensilvanicus had bias in only 2.0% and 2.3% of codon pairs, respectively, compared to the average 37.7%.

“However, Buchnera aphidicola and Candidatus blochmannia pensilvanicus had bias in only 2.0% and 2.3% of codon pairs, respectively, as compared to the average 37.7% (Figure 2).”

After removing the effects of single codon usage and dipeptide biases, a set of neighboring codon pairs has avoidances or preferences conserved in all three domains of life.

“After removing the effects of single codon usage and dipeptide biases we discovered a set of neighboring codons for which avoidances or preferences were conserved in all three domains of life.”

• Also stated in: § Background · plain

  “We show that certain codon context biases are conserved in the protein coding sequences of different species.”

Extending the distance between two codons (1-3, 1-4, 1-10) decreased the RDCU correlation.

“Extending the distance between two codons (1–3, 1–4, 1–10) decreased the RDCU correlation.”

Among preferred codon pairs, nnGCnn is the major type.

“Among the preferred codon pairs, nnGCnn was the major type.”

• Also stated in: § Over-represented codon pairs can be divided into 4 types · plain

  “The most abundant type of conserved over-represented codon pair was nnGCnn (Type 1P).”

Different patterns ranging from dinucleotides to hexanucleotides could explain conserved biased codon pair usage.

“However, our results showed that different patterns ranging from dinucleotides to hexanucleotides could explain conserved biased codon pair usage.”

Among different avoided sub-patterns causing conserved avoidance of codon pairs, the last nucleotide of the P-site codon in a pair was always fixed, with the exception of the pattern UnnnnU for codon pair UUUUUU.

“Interestingly, among the different avoided sub-patterns causing the conserved avoidance of codon pairs, the last nucleotide of the P-site codon in a pair was always fixed (the only exception was the pattern UnnnnU for codon pair UUUUUU).”

288 neighboring codon pairs were preferred or avoided in most of the organisms studied.

“On the basis of that criterion, we found 288 neighboring codon pairs (1–2 codon pairs) that were preferred or avoided in most of the organisms studied [Additional files 1, 2].”

81 codon pairs were over-represented in more than half the organisms studied.

“We found 81 codon pairs that were over-represented in more than half the organisms studied (Table 3, [additional file 2]).”

The most considerably biased conserved codon pairs are biased irrespective of phylogenetic class.

“Codon pair usage analysis showed that the most considerably biased conserved codon pairs are biased irrespective of phylogenetic class (Figures 1, 2, 3).”

Larger genomes appeared to contain larger fractions of biased codon pairs than smaller genomes.

“Indeed, larger genomes appeared to contain larger fractions of biased codon pairs than smaller genomes (Figure 4A).”

The highest correlation of RSCU occurred in the phylogenetically closest bacteria.

“As expected, the highest correlation of RSCU occurred in the phylogenetically closest bacteria.”

Avoidance of mononucleotide repeats such as GGGGGn, GGGGnn, nCCCCn and UUUUUU was conserved in most organisms (Type 8A).

“Avoidance of mononucleotide repeats such as GGGGGn, GGGGnn, nCCCCn and UUUUUU was also conserved in most organisms (Type 8A).”

Many nnUAnn type patterns contained codon pairs with stop codons in -1 frame on the sense strand (67%, 47/70).

“Many of the nnUAnn type patterns contained codon pairs with stop codons in -1 frame on the sense strand (67%, 47/70).”

The greatest similarity in RDCU among the species analyzed occurred when the calculation was based on 1-2 codon pairs.

“The greatest similarity in RDCU among the species analyzed occurred when the calculation was based on 1–2 codon pairs.”

Only three type 1A codon pairs did not contain out-frame UAA or UAG.

“Only three of the type 1A codon pairs did not contain out-frame UAA or UAG.”

Only a few clearly-separated phylogenetic classes occurred in both trees.

“However, only a few clearly-separated phylogenetic classes occurred in both trees.”

Aeropyrum pernix, Methanopyrus kandleri and Nanoarchaeum equitans had a considerable number of biased codon pairs.

“Aeropyrum pernix, Methanopyrus kandleri and Nanoarchaeum equitans had a considerable number of biased codon pairs (Figure 3), indicating that these organisms use a different set of biased codon pairs from the conserved set.”

No conserved biases were found for more distant codon pairs (1-4, 1-5).

“No conserved biases were found for more distant codon pairs.”

The most prevalent type of conserved preferred codon pair was nnGCnn.

“The most prevalent type of conserved preferred codon pair was nnGCnn [Additional file 5].”

A conserved biased set of codon pairs was found in a dataset covering a large number of organisms from the three domains of life.

“A conserved biased set of codon pairs was found in a dataset covering a large number of organisms from the three domains of life.”

Some genomes use sets of most avoided and most preferred codon pairs different from the conserved sets identified in this study.

“We also observed that some genomes use sets of most avoided and most preferred codon pairs different from the conserved sets identified in this study.”

All those codon pairs were more strongly avoided in ORFeomes than in genomes.

“All those codon pairs were more strongly avoided in ORFeomes than in genomes.”

The top 10 avoided and preferred codon pairs were not specific to any larger phylogenetic group.

“The top 10 avoided and preferred codon pairs were not specific to any larger phylogenetic group”

In some organisms with small genomes, only a few of those 20 codon pairs were significantly biased.

“However, in some organisms with small genomes, only a few of those 20 codon pairs were significantly biased.”

Many of the avoided nnUAnn patterns contained out-frame stop codons, UAA or UAG, on the sense strand.

“Many of the avoided nnUAnn patterns contained out-frame stop codons, UAA or UAG, on the sense strand.”

Among 9 groups of under-represented codon pairs found in our study the largest group was influenced by the avoidance of UA dinucleotides.

“Among 9 groups of under-represented codon pairs found in our study the largest group was also influenced by the avoidance of UA dinucleotides.”

There were eight mononucleotide repeats among the avoided codon pairs.

“There were eight mononucleotide repeats among the avoided codon pairs.”

Most of the pairs had stronger bias on the ORFeome level than on the whole genome level.

“Most of the pairs had stronger bias on the ORFeome level than on the whole genome level”

On the codon pair tree (RDCU tree), species are more distant from each other (codon pair usage is less similar).

“However, on the codon pair tree (RDCU tree), species are more distant from each other (codon pair usage is less similar).”

Larger phylogenetic groups are positioned together on the RDCU tree.

“In contrast, larger phylogenetic groups are positioned together on the RDCU tree.”

In 75.7% of cases the avoidance effect for nnUAnn codon pairs was stronger in ORFeomes than in genomes.

“The results showed that in 75.7% of cases the avoidance effect for nnUAnn codon pairs was stronger in ORFeomes than in genomes”

Several conserved preferred codon pairs were found.

“We also found several conserved preferred codon pairs.”

In the RSCU tree certain phylogenetic classes, for example bacilli, alpha- and gamma-proteobacteria, have extremely similar codon usage preferences within the classes.

“Tree analysis showed that in the RSCU tree certain phylogenetic classes, for example bacilli, alpha- and gamma-proteobacteria, have extremely similar codon usage preferences within the classes (Figure 6A).”

Most nnUAnn codon pairs also contained out-frame UAA and UAG triplets on the antisense strand.

“Interestingly, most nnUAnn codon pairs also contained out-frame UAA and UAG triplets on the antisense strand.”

The similarity of codon pair usage in eukaryotes is higher than the similarity of single codon usage.

“For example, the similarity of codon pair usage in eukaryotes is higher than the similarity of single codon usage (eukaryotes are placed together on the RDCU tree but not on the RSCU tree).”

The number of conserved preferred codon pairs was smaller than the number of avoided codon pairs.

“The number of conserved preferred codon pairs was smaller than the number of avoided codon pairs [Additional files 1, 2].”

The branch lengths in the codon pair usage tree are shorter than in the single codon usage tree.

“This was also confirmed by the shorter branch lengths in the codon pair usage tree than in the single codon usage tree (Figure 6).”

Sequences that are prone to frameshifting are successfully avoided in coding sequences.

“This means that sequences that are prone to frameshifting are successfully avoided in coding sequences.”

Conserved patterns result mainly from translational effects not from DNA-related mechanisms.

“Conserved patterns result mainly from translational effects not from DNA-related mechanisms since the biases are stronger in ORFeomes than in genomes.”

Aeropyrum pernix, Methanopyrus kandleri and Nanoarchaeum equitans use a different set of biased codon pairs from the conserved set.

“Aeropyrum pernix, Methanopyrus kandleri and Nanoarchaeum equitans had a considerable number of biased codon pairs (Figure 3), indicating that these organisms use a different set of biased codon pairs from the conserved set.”

Avoidance of nnUAnn codon pairs is partly related to out-frame stop codons.

“Thus, we assume that avoidance of nnUAnn codon pairs is partly related to out-frame stop codons.”

Expected codon pair values were normalized to dipeptide frequencies to ensure that observed codon pair effects were not caused by avoidances or preferences of dipeptides.

“To ensure that the effects observed at the codon pair level were not caused by avoidances or preferences of dipeptides, the expected codon pairs values were normalized to the dipeptide frequencies (see Methods).”

In addition to similar codon usage, these organisms use similar codon contexts.

“This indicates that in addition to similar codon usage, these organisms use similar codon contexts.”

Translational selection plays a major role in the avoidance of nnUAnn codon pairs.

“Thus we assume that translational selection plays a major role in the avoidance of these codon pairs.”

• Also stated in: § Under-represented codon pairs can be divided into 9 major types · hedged

  “This suggests that selection for nnUAnn avoidance occurs mainly at the translational level.”

Translational selection shapes codon pair usage in protein coding sequences by rules that are common to all three domains of life.

“Translational selection shapes codon pair usage in protein coding sequences by rules that are common to all three domains of life.”

The magnitude of effects of pentamers, tetramers, trimers and dimers cannot be compared directly with that of codon pairs because the number and variation in magnitude of effect differ markedly among sub-patterns of different lengths.

“Unfortunately, the magnitude of the effects (observed/expected ratio) of pentamers, tetramers, trimers and dimers cannot be compared directly with that of codon pairs because the number, and therefore the variation in magnitude of effect, differs markedly among sub-patterns of different lengths [Additional file 3].”

The common preference of codon pairs detected is mainly influenced by translational mechanisms.

“All the major types were more strongly over-represented in ORFeomes than in genomes, again indicating that the common preference of codon pairs that we detected is mainly influenced by translational mechanisms.”

Avoidance of the UA dinucleotide between two codons also has a role in nnUAnn avoidance, because out-frame UGA stop-codons were not observed in any conserved biased dicodon pairs.

“On the other hand, avoidance of the UA dinucleotide between two codons also has a role here, because out-frame UGA stop-codons were not observed in any of the conserved biased dicodon pairs.”

Those three type 1A codon pairs may not be related to the same kind of avoidances as all other type 1A codon pairs.

“Those three pairs may not be related to the same kind of avoidances as all other type 1A codon pairs [Additional file 4].”

B. aphidicola and C. blochmannia seem effectively to lack biased codon pairs.

“Therefore, these two genomes seem effectively to lack biased codon pairs.”

Certain codon contexts are strongly conserved over all domains of life.

“Our findings suggest that certain codon contexts are strongly conserved over all domains of life.”

Between different eukaryotes (mostly fungi) the similarity in codon context is greater than the similarity in codon usage.

“This suggests that between different eukaryotes (which in our dataset were mostly represented by fungi) the similarity in codon context is greater than the similarity in codon usage.”

Most conserved codon context biases are probably influenced by translational rather than DNA-related mechanisms.

“Most of them are probably influenced by translational rather than DNA-related mechanisms.”

The under- and over-represented codon pairs are indeed uniformly distributed.

“This indicates that the under- and over-represented codon pairs are indeed uniformly distributed.”

Codon pair usage bias can be distributed in many different ways.

“We conclude that codon pair usage bias can be distributed in many different ways.”

Interactions between the ribosomal E- and A-sites do not influence the codon context as much as interactions between the P- and A-sites.

“indicating that interactions between the ribosomal E- and A-sites do not influence the codon context as much as interactions between the P- and A-sites.”

The stronger avoidance of nnUAnn codon pairs in ORFeomes than in genomes suggests the influence of translational mechanisms.

“suggesting the influence of translational mechanisms (Table 2).”

Bias might also be observed in codon pair usage where codons are separated by three nucleotides (the 1-3 pair).

“Therefore, bias might also be observed in codon pair usage where codons are separated by three nucleotides (the 1–3 pair).”

tRNA concentration is a major selective force on codon usage patterns.

“suggesting that this is a major selective force on codon usage patterns [31-33].”

• cites [31] Dong H, Nilsson L, Kurland CG: Co-variation of tRNA abundance and codon usage in Escherichia coli at different growth rates. J Mol Biol. 1996, 260 (5): 649-663. 10.1006/jmbi.1996.0428. sourceNot checked — no full text of the source
• cites [32] Ikemura T: Correlation between the abundance of Escherichia coli transfer RNAs and the occurrence of the respective codons in its protein genes. J Mol Biol. 1981, 146 (1): 1-21. 10.1016/0022-2836(81)90363-6. sourceNot checked — no full text of the source
• cites [33] Elf J, Nilsson D, Tenson T, Ehrenberg M: Selective charging of tRNA isoacceptors explains patterns of codon usage. Science. 2003, 300 (5626): 1718-1722. 10.1126/science.1083811. sourceNot checked — no full text of the source

The observation that only the stop codons UAA and UAG were avoided suggests that this kind of misreading might be caused by termination factor 1.

“The observation that only the stop codons UAA and UAG were avoided suggests that this kind of misreading might be caused by termination factor 1, the protein responsible for decoding them.”

Out-frame stop codons influence the avoidance of nnUAnn codon pairs.

“This indicates that out-frame stop codons influence the avoidance of nnUAnn codon pairs.”

Translation has a greater influence on codon pair biases than molecular mechanisms that shape the genomic DNA in general.

“suggesting that translation has a greater influence on codon pair biases than molecular mechanisms that shape the genomic DNA in general.”

Such contexts should be selected against in protein coding sequences.

“Therefore, such contexts should be selected against in protein coding sequences.”

This bias could also be species specific among bacteria and eukaryotes.

“Our results correlate with that and suggest that this bias could also be species specific among bacteria and eukaryotes.”

Usage of those top 10 avoided and preferred codon pairs is universally conserved.

“suggesting that usage of those codon pairs is universally conserved (Figures 2 and 3).”

nnUAnn type avoidances are related to translational mechanisms.

“However, our results suggest that nnUAnn type avoidances are related to translational mechanisms because they are stronger in ORFeomes than in genomes.”

Those codon pairs were avoided to reduce the frequency of frameshifting events in polynucleotide sequences.

“This suggests that they were avoided to reduce the frequency of frameshifting events in polynucleotide sequences.”

Codon frequencies correlate with tRNA concentrations.

“Codon frequencies correlate with tRNA concentrations, suggesting that this is a major selective force on codon usage patterns [31-33].”

• cites [31] Dong H, Nilsson L, Kurland CG: Co-variation of tRNA abundance and codon usage in Escherichia coli at different growth rates. J Mol Biol. 1996, 260 (5): 649-663. 10.1006/jmbi.1996.0428. sourceNot checked — no full text of the source
• cites [32] Ikemura T: Correlation between the abundance of Escherichia coli transfer RNAs and the occurrence of the respective codons in its protein genes. J Mol Biol. 1981, 146 (1): 1-21. 10.1016/0022-2836(81)90363-6. sourceNot checked — no full text of the source
• cites [33] Elf J, Nilsson D, Tenson T, Ehrenberg M: Selective charging of tRNA isoacceptors explains patterns of codon usage. Science. 2003, 300 (5626): 1718-1722. 10.1126/science.1083811. sourceNot checked — no full text of the source

Certain codon contexts are markedly conserved over all domains of life.

“Our findings suggest that certain codon contexts are markedly conserved over all domains of life.”

Codon preference and codon pair preference are shaped by different molecular mechanisms.

“The large differences between the RSCU and RDCU tree topologies and branch lengths imply that codon preference and codon pair preference are shaped by different molecular mechanisms.”