Fimmel Elena, Gumbel Markus, Starman Martin, Strüngmann Lutz
Center for Algorithmic and Mathematical Methods in Medicine, Biology, and Biotechnology, Mannheim University of Applied Sciences, 68163 Mannheim, Germany.
Life (Basel). 2021 Dec 3;11(12):1338. doi: 10.3390/life11121338.
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.
人们认为，标准遗传密码（SGC）的密码子 - 氨基酸分配有助于将点突变所造成的负面影响降至最低。遗传密码的所有可能点突变都可以表示为一个加权图，其权重对应于这些突变的概率。然后，可以通过所谓的电导度量来描述密码针对点突变的稳健性。本文对摆动效应进行了量化，此前曾通过应用加权图方法对其进行研究，并使用进化优化算法寻找最优权重，以最大化密码的稳健性。我们研究的一个结果是，遗传密码的稳健性受第三位突变的影响最小——如同摆动效应一样。此外，结果清楚地表明，密码子第一位，甚至更重要的是第二位的点突变对遗传密码的稳健性有非常大的影响。将这些结果与编码序列中的单核苷酸变异（SNV）进行了比较，这些变异支持了我们的发现。此外，还分析了在稳健性最大化时，从随机密码表进化而来的遗传密码结构。我们的计算表明，所得的密码表与标准遗传密码非常接近。总之，结果表明，针对点突变的稳健性似乎是标准遗传密码进化中的一个重要因素。
