Studies of Mutation Accumulation in Three Codon Positions using Monte Carlo Simulations and Metropolis-Hastings Algorithm

Protein coding sequences are characterized by specific nucleotide composition in three codon positions as a result of mutational and selection pressures. To analyse the impact of mutations and different transi-tion/ transversion ratio on three codon position in protein coding sequences, we elaborated a model of genome evolution based Monte Carlo simulation. Selection was applied against stop translation codons and modified Metropolis-Hastings algorithm to maintain typical nucleotide composition of particular codon positions. The simulations were performed on genomes consisting of bacterial gene sequences. We used a series of nucleotide substitution matrices assuming different transition/ transversion ratio and nucleotide stationary distribution characteristic of the real mutational pressure. The simulations showed exponential decrease in the number of eliminated genomes with the growth of the transition/ transversion ratio. The same trend was also observed both for accepted and to lesser extent for rejected mutations. The third codon positions much more mutations accepted than rejected because of very similar composition to the mutational stationary distribution, whereas the first positions accumulated the smallest number of mutations and rejected the most as a result of strong selection on its nucleotide composition. The obtained results showed different response of three codon positions on mutational pressure related with their characteristic nucleotide composition.