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”.

Keywords

• Standard genetic code
• Overlapping codes
• Frameshift mutation
• Polar requirement