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Implications of fidelity difference between the leading and the lagging strand of DNA for the acceleration of evolution.

Furusawa M - Front Oncol (2012)

Bottom Line: From the viewpoint of the fidelity difference between the leading and the lagging strand, the basic conditions for the acceleration of evolution are examined.The plausible molecular mechanism for the faster molecular clocks observed in birds and mammals is discussed, with special reference to the accelerated evolution in the past.Possible applications in different fields are also discussed.

View Article: PubMed Central - PubMed

Affiliation: Neo-Morgan Laboratory Incorporated, Biotechnology Research Center Kawasaki, Japan.

ABSTRACT
Without exceptions, genomic DNA of living organisms is replicated using the leading and the lagging strand. In a conventional idea of mutagenesis accompanying DNA replication, mutations are thought to be introduced stochastically and evenly into the two daughter DNAs. Here, however, we hypothesized that the fidelity of the lagging strand is lower than that of the leading strand. Our simulations with a simplified model DNA clearly indicated that, even if mutation rates exceeded the so-called threshold values, an original genotype was guaranteed in the pedigree and, at the same time, the enlargement of diversity was attained with repeated generations. According to our lagging-strand-biased-mutagenesis model, mutator microorganisms were established in which mutations biased to the lagging strand were introduced by deleting the proofreading activity of DNA polymerase. These mutators ("disparity mutators") grew normally and had a quick and extraordinarily high adaptability against very severe circumstances. From the viewpoint of the fidelity difference between the leading and the lagging strand, the basic conditions for the acceleration of evolution are examined. The plausible molecular mechanism for the faster molecular clocks observed in birds and mammals is discussed, with special reference to the accelerated evolution in the past. Possible applications in different fields are also discussed.

No MeSH data available.


Related in: MedlinePlus

The distribution of individuals with a given number of mutations in the tenth generation for the parity (A) and disparity(B) stochastic models is shown. The results of 12 trials of simulations are shown. For details see text. Adapted from Furusawa and Doi (1992).
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Figure 2: The distribution of individuals with a given number of mutations in the tenth generation for the parity (A) and disparity(B) stochastic models is shown. The results of 12 trials of simulations are shown. For details see text. Adapted from Furusawa and Doi (1992).

Mentions: We compared the distribution of mutations in a parity model (average two mutations/replication being introduced into the leading and the lagging strands) with that of a disparity model (average 1.99 mutations in the lagging strand and 0.01 mutations in the leading strand). For the simulation of this stochastic model, a binominal distribution was used. Figure 2 summarizes the results of 12 trials at the 10th generation. Figure 2A shows the distribution of mutants in the parity model. There is no individual with zero-mutations. In contrast, as shown in Figure 2B, the disparity model shows a very flat distribution. The ancestral individuals with zero-mutations are always observable except in the ninth trial and highly mutated mutants comparable with the parity model are produced (Furusawa and Doi, 1992). This flat distribution of mutants including ancestral individuals in the disparity model is expected from the pedigree of the deterministic disparity model shown in Figure 1.


Implications of fidelity difference between the leading and the lagging strand of DNA for the acceleration of evolution.

Furusawa M - Front Oncol (2012)

The distribution of individuals with a given number of mutations in the tenth generation for the parity (A) and disparity(B) stochastic models is shown. The results of 12 trials of simulations are shown. For details see text. Adapted from Furusawa and Doi (1992).
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC3472163&req=5

Figure 2: The distribution of individuals with a given number of mutations in the tenth generation for the parity (A) and disparity(B) stochastic models is shown. The results of 12 trials of simulations are shown. For details see text. Adapted from Furusawa and Doi (1992).
Mentions: We compared the distribution of mutations in a parity model (average two mutations/replication being introduced into the leading and the lagging strands) with that of a disparity model (average 1.99 mutations in the lagging strand and 0.01 mutations in the leading strand). For the simulation of this stochastic model, a binominal distribution was used. Figure 2 summarizes the results of 12 trials at the 10th generation. Figure 2A shows the distribution of mutants in the parity model. There is no individual with zero-mutations. In contrast, as shown in Figure 2B, the disparity model shows a very flat distribution. The ancestral individuals with zero-mutations are always observable except in the ninth trial and highly mutated mutants comparable with the parity model are produced (Furusawa and Doi, 1992). This flat distribution of mutants including ancestral individuals in the disparity model is expected from the pedigree of the deterministic disparity model shown in Figure 1.

Bottom Line: From the viewpoint of the fidelity difference between the leading and the lagging strand, the basic conditions for the acceleration of evolution are examined.The plausible molecular mechanism for the faster molecular clocks observed in birds and mammals is discussed, with special reference to the accelerated evolution in the past.Possible applications in different fields are also discussed.

View Article: PubMed Central - PubMed

Affiliation: Neo-Morgan Laboratory Incorporated, Biotechnology Research Center Kawasaki, Japan.

ABSTRACT
Without exceptions, genomic DNA of living organisms is replicated using the leading and the lagging strand. In a conventional idea of mutagenesis accompanying DNA replication, mutations are thought to be introduced stochastically and evenly into the two daughter DNAs. Here, however, we hypothesized that the fidelity of the lagging strand is lower than that of the leading strand. Our simulations with a simplified model DNA clearly indicated that, even if mutation rates exceeded the so-called threshold values, an original genotype was guaranteed in the pedigree and, at the same time, the enlargement of diversity was attained with repeated generations. According to our lagging-strand-biased-mutagenesis model, mutator microorganisms were established in which mutations biased to the lagging strand were introduced by deleting the proofreading activity of DNA polymerase. These mutators ("disparity mutators") grew normally and had a quick and extraordinarily high adaptability against very severe circumstances. From the viewpoint of the fidelity difference between the leading and the lagging strand, the basic conditions for the acceleration of evolution are examined. The plausible molecular mechanism for the faster molecular clocks observed in birds and mammals is discussed, with special reference to the accelerated evolution in the past. Possible applications in different fields are also discussed.

No MeSH data available.


Related in: MedlinePlus