Optimization of the standard genetic code according to three codon positions using an evolutionary algorithm

Abstract

Many biological systems are typically examined from the point of view of adaptation to certain conditions or requirements. One such system is the standard genetic code (SGC), which generally minimizes the cost of amino acid replacements resulting from mutations or mistranslations. However, no full consensus has been reached on the factors that caused the evolution of this feature. One of the hypotheses suggests that code optimality was directly selected as an advantage to preserve information about encoded proteins. An important feature that should be considered when studying the SGC is the different roles of the three codon positions. Therefore, we investigated the robustness of this code regarding the cost of amino acid replacements resulting from substitutions in these positions separately and the sum of these costs. We applied a modified evolutionary algorithm and included four models of the genetic code assuming various restrictions on its structure. The SGC was compared both with the codes that minimize the objective function and those that maximize it. This approach allowed us to place the SGC in the global space of possible codes, which is a more appropriate and unbiased comparison than that with randomly generated codes because they are characterized by relatively uniform amino acid assignments to codons. The SGC appeared to be well optimized at the global scale, but its individual positions were not fully optimized because there were codes that were optimized for only one codon position and simultaneously outperformed the SGC at the other positions. We also found that different code structures may lead to the same optimality and that random codes can show a tendency to minimize costs under some of the genetic code models. Our results suggest that the optimality of SGC could be a by-product of other processes.

The influence of different types of translational inaccuracies on the genetic code structure

“…In terms of minimization of amino acid replacements resulting from point mutations in codons, measured here by the average conductance, the SGC is placed between the M 1 codes, characterized by the lowest conductance, and the codes from the M 2 and M 3 models. In agreement with our simulation study, other analyses also showed that the SGC is not perfectly optimized in this respect and better codes can be found [11,44,50,57,58,[87][88][89]. Therefore, it is possible that the assignments of amino acids to codons occurred in accordance with other mechanisms, while the minimization of mutation errors was adjusted by the direct optimization of the mutational pressure around the established genetic code [90][91][92][93][94].…”

Some theoretical aspects of reprogramming the standard genetic code

“…This assumption follows the adaptation hypothesis, which claims that the SGC evolved to minimize harmful consequences of mutations or mistranslations of coded proteins [Woese, 1965, Sonneborn, 1965, Epstein, 1966, Goldberg and Wittes, 1966, Haig and Hurst, 1991, Freeland and Hurst, 1998, Freeland et al, 2000, Gilis et al, 2001. Although this code did not turn out perfectly optimized in this respect [B lażej et al, 2018a, B lażej et al, 2016, Massey, 2008, Novozhilov et al, 2007, Santos et al, 2011, Santos and Monteagudo, 2017, B lażej et al, 2018b, B lażej et al, 2019b, Wnetrzak et al, 2019, it shows a general tendency to error minimization in the global scale. This property is better exhibited by its alternative versions [B lażej et al, 2018c, B lażej et al, 2019a], which occurred later in the evolution.…”

Comparative genome analysis reveals a distinct influence of nucleotide composition on virus–host species‐specific interaction of prawn‐infecting nodavirus

“…A non-synonymous change may occur in a coding sequence that is most likely due to the mutation at second codon position as the site is the most functionally constrained. Subsequently, the course of evolution will occur at the protein level and its variation is constrained by functional selection (Błażej, Wnętrzak, Mackiewicz, & Mackiewicz, 2018). In fact, the third codon position which regards as synonymous codon site and the least functionally constrained may be in fourfold degenerate via a certain combination of the nucleotide at first and second codon positions (Wald, Alroy, Botzman, & Margalit, 2012).…”