Computational Analysis of Genetic Code Variations Optimized for the Robustness against Point Mutations with Wobble-like Effects

Abstract

It is believed that the codon–amino acid assignments of the standard genetic code (SGC) help to minimize the negative effects caused by point mutations. All possible point mutations of the genetic code can be represented as a weighted graph with weights that correspond to the probabilities of these mutations. The robustness of a code against point mutations can be described then by means of the so-called conductance measure. This paper quantifies the wobble effect, which was investigated previously by applying the weighted graph approach, and seeks optimal weights using an evolutionary optimization algorithm to maximize the code’s robustness. One result of our study is that the robustness of the genetic code is least influenced by mutations in the third position—like with the wobble effect. Moreover, the results clearly demonstrate that point mutations in the first, and even more importantly, in the second base of a codon have a very large influence on the robustness of the genetic code. These results were compared to single nucleotide variants (SNV) in coding sequences which support our findings. Additionally, it was analyzed which structure of a genetic code evolves from random code tables when the robustness is maximized. Our calculations show that the resulting code tables are very close to the standard genetic code. In conclusion, the results illustrate that the robustness against point mutations seems to be an important factor in the evolution of the standard genetic code.

Rules governing the genetic code degeneracy/redundancy and spatial organization of the codon informative properties

“…Some of these studies were devoted to studying these interactions through molecular dynamics simulations in order to analyze the forces acting between adjacent atoms (36,37). Other evolutionary analyses have focused on the role natural selection could have played in shaping a robust code, minimizing the impact of mutations and mistranslation on protein structure and function (38)(39)(40)(41)(42). This phenomenon is closely associated with codon usage (43)(44)(45).…”