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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 mutant distribution in “quasi-species” as a function of the mean error rate (m) per genome. The genome has a binary base sequence of 50. c is the relative concentration of error-free polymerase. The sum of the relative stationary concentration of the wild-type sequence with zero-mutations (I0), of all one-error mutants (I1), of all two-error mutants (I2), etc. are plotted. (A)c = 0 or the parity model; (B)c = 0.09; (C)c = 0.1; and (D)c = 0.3. Arrow indicates the error threshold. For details see text. Adapted from Aoki and Furusawa (2003); permitted to use this figure from APS Journal, ASP Copyright 2003.
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Figure 5: The mutant distribution in “quasi-species” as a function of the mean error rate (m) per genome. The genome has a binary base sequence of 50. c is the relative concentration of error-free polymerase. The sum of the relative stationary concentration of the wild-type sequence with zero-mutations (I0), of all one-error mutants (I1), of all two-error mutants (I2), etc. are plotted. (A)c = 0 or the parity model; (B)c = 0.09; (C)c = 0.1; and (D)c = 0.3. Arrow indicates the error threshold. For details see text. Adapted from Aoki and Furusawa (2003); permitted to use this figure from APS Journal, ASP Copyright 2003.

Mentions: Eigen’s group demonstrated the existence of a critical error threshold using a model RNA (Eigen et al., 1989). Different kinds of RNA polymerase having various fidelities were provided, and each of them was added into a reactor respectively. When the replication reaction reached a stable state, the number of mutations in each RNA molecule was calculated. With increasing error rates of error-prone polymerase, the number of the RNA molecules carrying more mutations naturally increased. Finally, the error rate increased to a critical point just before the genetic information being melted away (the “edge-of-chaos”). If the mutation rate exceeds the critical value, the population immediately falls into a deep chaotic sea, i.e., death (Figure 5A).


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

Furusawa M - Front Oncol (2012)

The mutant distribution in “quasi-species” as a function of the mean error rate (m) per genome. The genome has a binary base sequence of 50. c is the relative concentration of error-free polymerase. The sum of the relative stationary concentration of the wild-type sequence with zero-mutations (I0), of all one-error mutants (I1), of all two-error mutants (I2), etc. are plotted. (A)c = 0 or the parity model; (B)c = 0.09; (C)c = 0.1; and (D)c = 0.3. Arrow indicates the error threshold. For details see text. Adapted from Aoki and Furusawa (2003); permitted to use this figure from APS Journal, ASP Copyright 2003.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 5: The mutant distribution in “quasi-species” as a function of the mean error rate (m) per genome. The genome has a binary base sequence of 50. c is the relative concentration of error-free polymerase. The sum of the relative stationary concentration of the wild-type sequence with zero-mutations (I0), of all one-error mutants (I1), of all two-error mutants (I2), etc. are plotted. (A)c = 0 or the parity model; (B)c = 0.09; (C)c = 0.1; and (D)c = 0.3. Arrow indicates the error threshold. For details see text. Adapted from Aoki and Furusawa (2003); permitted to use this figure from APS Journal, ASP Copyright 2003.
Mentions: Eigen’s group demonstrated the existence of a critical error threshold using a model RNA (Eigen et al., 1989). Different kinds of RNA polymerase having various fidelities were provided, and each of them was added into a reactor respectively. When the replication reaction reached a stable state, the number of mutations in each RNA molecule was calculated. With increasing error rates of error-prone polymerase, the number of the RNA molecules carrying more mutations naturally increased. Finally, the error rate increased to a critical point just before the genetic information being melted away (the “edge-of-chaos”). If the mutation rate exceeds the critical value, the population immediately falls into a deep chaotic sea, i.e., death (Figure 5A).

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