On the efficiency of the Genetic Code after frameshift mutations

Abstract

Statistical and biochemical studies of the standard genetic code (SGC) have found evidence that the impact of mistranslations is minimized in a way that erroneous codes are either synonymous or code for an amino acid with similar polarity as the originally coded amino acid. It could be quantified that the SGC is optimized to protect this specific chemical property as good as possible. In recent work, it has been speculated that the multilevel optimization of the genetic code stands in the wider context of overlapping codes. This work tries to follow the systematic approach on mistranslations and to extend those analyses to the general effect of frameshift mutations on the polarity conservation of amino acids: We generated one million random codes and compared their average polarity change over all triplets and the whole set of possible frameshift mutations. While the natural code -just as for the point mutations -appears to be competitively robust against frameshift mutations as well, we found that both optimizations appear to be independent of each other. For both, better codes can be found, but it becomes significantly more difficult to find candidates that optimize all of these features -just like the SGC does. We conclude that the SGC is not only very efficient in minimizing the consequences of mistranslations, but rather optimized in amino acid polarity conservation for all three effects of code alteration, namely translational errors, point and frameshift mutations. In other words, our result demonstrates that the SGC appears to be much more than just "one in a million".

Theoretical minimal RNA rings mimick molecular evolution before tRNA-mediated translation: codon-amino acid affinities increase from early to late RNA rings

“…This fits with observations suggesting that overlap coding is a common property of genes [59][60][61][62][63][64][65][66][67]. Indeed, the genetic code is optimized for coding after frameshifts [1,[65][66][67].…”

“…Codon-amino acid assignments according to the genetic code are not random [1] because many codon and anticodon properties correlate with properties of cognate amino acids [2][3][4]. Numerous analyses indicate the genetic code minimizes error impacts for various processes and properties: mutations on protein structure [5,6], how proteins fold [7][8][9], tRNA misloading by tRNA synthetases [10][11][12][13], frameshifts during translation before and after these occur (before occurrence [14][15][16][17], after occurrence [18][19][20][21][22][23]). The genetic code maximizes the diversity of physicochemical properties of coded amino acids [24,25] and optimizes error according to several properties at the same time [1].…”

Directed Mutations Recode Mitochondrial Genes: From Regular to Stopless Genetic Codes

“…For example, one can expect that frameshift tolerance biases exist for identity at amino acids that are not easily replaced by other amino acids (e.g., cysteine), but less for mutable ones (leucine, isoleucine, etc.). The preliminary tests presented here are not incompatible with the frameshift tolerance hypothesis [83][84][85].…”

“…Several effects could explain that results are not very strong statistically at the level of redundancy between frames. This hypothesis should be further tested, experimentally as done by Wang et al [83][84][85] and by other bioinformatics analyses. For example, one can expect that frameshift tolerance biases exist for identity at amino acids that are not easily replaced by other amino acids (e.g., cysteine), but less for mutable ones (leucine, isoleucine, etc.).…”

“…The original hypothesis of frame shiftability suggests that different frames of a gene code for somewhat similar peptides, presumably because the genetic code is optimized to tolerate frameshifts [83][84][85]. This hypothesis suggests that redundancy among frames in Aleurodicus dispersus should be greater than in the closely related Aleurodicus dugesii where coding seems regular, assuming that changes in coding structure increase redundancy among frames for coding protein variants with similar functions.…”