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A Protocol for Functional Assessment of Whole-Protein Saturation Mutagenesis Libraries Utilizing High-Throughput Sequencing
Published on: July 3, 2016
Optimization of Mutation Pressure in Relation to Properties of Protein-Coding Sequences in Bacterial Genomes
Paweł Błażej1, Błażej Miasojedow2, Małgorzata Grabińska1
1Department of Genomics, Faculty of Biotechnology, University of Wrocław, Wrocław, Poland.
Abstract:
Most mutations are deleterious and require energetically costly repairs. Therefore, it seems that any minimization of mutation rate is beneficial. On the other hand, mutations generate genetic diversity indispensable for evolution and adaptation of organisms to changing environmental conditions. Thus, it is expected that a spontaneous mutational pressure should be an optimal compromise between these two extremes. In order to study the optimization of the pressure, we compared mutational transition probability matrices from bacterial genomes with artificial matrices fulfilling the same general features as the real ones, e.g., the stationary distribution and the speed of convergence to the stationarity. The artificial matrices were optimized on real protein-coding sequences based on Evolutionary Strategies approach to minimize or maximize the probability of non-synonymous substitutions and costs of amino acid replacements depending on their physicochemical properties. The results show that the empirical matrices have a tendency to minimize the effects of mutations rather than maximize their costs on the amino acid level. They were also similar to the optimized artificial matrices in the nucleotide substitution pattern, especially the high transitions/transversions ratio. We observed no substantial differences between the effects of mutational matrices on protein-coding sequences in genomes under study in respect of differently replicated DNA strands, mutational cost types and properties of the referenced artificial matrices. The findings indicate that the empirical mutational matrices are rather adapted to minimize mutational costs in the studied organisms in comparison to other matrices with similar mathematical constraints.
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