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However, the most frequent codons do not always correspond with their cognates in the mitochondrial tRNAs (see Additional file 4).
Overall, TTT (Phe), TTG (Leu) and TTA (Leu) are the most frequent codons, a result consistent with other invertebrate mtDNAs [ 34].
The most frequent codons have the highest relative adaptiveness towards its host, and sequences with higher CAIs are suggested to be preferred over those with lower CAIs [ 27].
For assessing codon usage patterns, we calculated the Codon Adaptation Index (CAI), a measure of codon optimality [ 29], for every ORF with respect to the most frequent codons occurring in S. coelicolor.
The unusual codon frequency points to a selection pressure on the tRNA translation system to codon-anticodon sequences of highest versatility instead of showing adaptations in anticodon sequences to the most frequent codons.
Therefore, the reverse complements of the anticodon sequences show usually the low frequent codons (Table 2) rejecting an adaptation of the anticodon sequences to most frequent codons (see [ 17]).
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UUU (phenylalanine) is the most frequent codon, followed by UUA (leucine).
The most frequent codon on the majority strands is TTT (Phe), and on the minority strand is ATA (Met), highlighting asymmetric strand bias.
This comparison to the authentic sequences revealed significant divergences from most frequent codon usage in addition to the selected consensus sequence.
Alternatively, the "theory of codon-anticodon adaptation" suggests that the anticodon sequence of a tRNA gene is adapted to the most frequent codon among all the recognized codons [ 19, 20].
The eight KRAS codon 61 mutations present in our series result in four different amino acid substitutions (p.Gln61His, p.Gln61Lys, p.Gln61Leu, and p.Gln61Arg), with the p.Gln61Leu being the most frequent codon 61 mutation in this series (37.5%; 3/8).
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