High correlation between the turnover of nucleotides under mutational pressure and the DNA composition.
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However, it is important to discriminate between the effect of mutations, and the effect of selection, when studying the phylogenic relations between taxa.We have tested in computer simulations, and analytically, the available substitution matrices for many genomes, and we have found that DNA strands in equilibrium under mutational pressure have unique feature: the fraction of each type of nucleotide is linearly dependent on the time needed for substitution of half of nucleotides of a given type, with a correlation coefficient close to 1.Substitution matrices found for sequences under selection pressure do not have this property.
Affiliation: Institute of Microbiology, Wroclaw University, ul Przybyszewskiego 63/77, 51-148 Wroclaw, Poland. kowal@microb.uni.wroc.pl
ABSTRACT
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Background: Any DNA sequence is a result of compromise between the selection and mutation pressures exerted on it during evolution. It is difficult to estimate the relative influence of each of these pressures on the rate of accumulation of substitutions. However, it is important to discriminate between the effect of mutations, and the effect of selection, when studying the phylogenic relations between taxa. Results: We have tested in computer simulations, and analytically, the available substitution matrices for many genomes, and we have found that DNA strands in equilibrium under mutational pressure have unique feature: the fraction of each type of nucleotide is linearly dependent on the time needed for substitution of half of nucleotides of a given type, with a correlation coefficient close to 1. Substitution matrices found for sequences under selection pressure do not have this property. A substitution matrix for the leading strand of the Borrelia burgdorferi genome, having reached equilibrium in computer simulation, gives a DNA sequence with nucleotide composition and asymmetry corresponding precisely to the third positions in codons of protein coding genes located on the leading strand. Conclusions: Parameters of mutational pressure allow us to count DNA composition in equilibrium with this mutational pressure. Comparing any real DNA sequence with the sequence in equilibrium it is possible to estimate the distance between these sequences, which could be used as a measure of the selection pressure. Furthermore, the parameters of the mutational pressure enable direct estimation of the relative mutation rates in any DNA sequence in the studied genome. Related in: MedlinePlus |
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Mentions: Note that there are numbers, not frequencies in the equations. Fulfilling these equations means that the nucleotide composition of the sequences submitted to the mutational pressure determined by the parameters of BbTS is in equilibrium. We have assumed that in the case of the B. burgdorferi genome the best approximation of such sequences is the composition of the third positions of codons of ORFs, as has been argued in the Introduction section. Thus, the nucleotide composition of this set of nucleotides should not change significantly under such mutational pressure. To prove that, we simulated the mutational pressure on the sequence of the same composition as described previously [19] and after 10,000 Monte Carlo Steps (MCS), when the sequence was in equilibrium, we compared it to the sequence before the simulation. The ratios of nucleotides were 0.994, 1.008, 0.992 and 0.988 for A, T, G, and C, respectively (note that the ratios do not sum to 1 because they are not weighted). There are no significant changes in nucleotide composition of the third positions after the prolonged exposition to the mutational pressure described by BbTS (Chi square test, p = 0.99987). Thus, BbTS generates DNA sequence with nucleotide composition corresponding precisely to the nucleotide composition of the third codon positions. In Fig. 1 we have shown the evolution of two DNA sequences, of which one originally had equimolar nucleotide composition and the other one – the nucleotide composition of the third codon positions of ORFs from the leading strand. Both sequences reach the same final nucleotide composition. Furthermore, a sequence obtained after long evolution in computer has very similar asymmetry in terms of GC skew and AT skew as the sequence of the third codon positions before evolution. GC skew is [G-C]/ [G+C] and AT skew is [A-T]/ [A+T]. The AT skew is -0.23 and -0.22 for the sequences before and after simulation, respectively. The GC skew is 0.34 for the sequences before and after simulation. Note that the most frequent substitution is C->T transition, which is in agreement with the cytosine deamination theory (see ref. 10 and references therein), and the average transition frequency is twofold higher than transversion frequency. |
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Affiliation: Institute of Microbiology, Wroclaw University, ul Przybyszewskiego 63/77, 51-148 Wroclaw, Poland. kowal@microb.uni.wroc.pl
Background: Any DNA sequence is a result of compromise between the selection and mutation pressures exerted on it during evolution. It is difficult to estimate the relative influence of each of these pressures on the rate of accumulation of substitutions. However, it is important to discriminate between the effect of mutations, and the effect of selection, when studying the phylogenic relations between taxa.
Results: We have tested in computer simulations, and analytically, the available substitution matrices for many genomes, and we have found that DNA strands in equilibrium under mutational pressure have unique feature: the fraction of each type of nucleotide is linearly dependent on the time needed for substitution of half of nucleotides of a given type, with a correlation coefficient close to 1. Substitution matrices found for sequences under selection pressure do not have this property. A substitution matrix for the leading strand of the Borrelia burgdorferi genome, having reached equilibrium in computer simulation, gives a DNA sequence with nucleotide composition and asymmetry corresponding precisely to the third positions in codons of protein coding genes located on the leading strand.
Conclusions: Parameters of mutational pressure allow us to count DNA composition in equilibrium with this mutational pressure. Comparing any real DNA sequence with the sequence in equilibrium it is possible to estimate the distance between these sequences, which could be used as a measure of the selection pressure. Furthermore, the parameters of the mutational pressure enable direct estimation of the relative mutation rates in any DNA sequence in the studied genome.