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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

Results of the simulation with the “neo-Darwinian genetic algorithm” in the diploid and sexual world are shown.(A) Disparity individuals with mutation rate (n) = 0.1. Green, no crossover; blue, crossover frequency (CF) = 0.2/chromosome; red, CF = 2.0; and black, asexual and diploid. (B) Disparity individuals n = 8.0. Green, no crossover: blue, CF = 0.2; red, CF = 2.0; and black, asexual. (C) Parity individuals n = 0.1. Green, no crossover; blue, CF = 0.2; red, CF = 2.0; and black, asexual. (D) Parity individual with various mutation rates. Black, n = 2.0 without crossover; magenta, n = 2.32 without crossover; cyan, n = 2.32 and CF = 2.0; red, n = 2.4 without crossover; and blue, n = 2.4 and CF = 2.0. Adapted from Wada et al. (1993); Copyright 1993, National Academy of Sciences, USA.
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Figure 4: Results of the simulation with the “neo-Darwinian genetic algorithm” in the diploid and sexual world are shown.(A) Disparity individuals with mutation rate (n) = 0.1. Green, no crossover; blue, crossover frequency (CF) = 0.2/chromosome; red, CF = 2.0; and black, asexual and diploid. (B) Disparity individuals n = 8.0. Green, no crossover: blue, CF = 0.2; red, CF = 2.0; and black, asexual. (C) Parity individuals n = 0.1. Green, no crossover; blue, CF = 0.2; red, CF = 2.0; and black, asexual. (D) Parity individual with various mutation rates. Black, n = 2.0 without crossover; magenta, n = 2.32 without crossover; cyan, n = 2.32 and CF = 2.0; red, n = 2.4 without crossover; and blue, n = 2.4 and CF = 2.0. Adapted from Wada et al. (1993); Copyright 1993, National Academy of Sciences, USA.

Mentions: The results are representatively shown in Figure 4. At the low mutation rate (0.1), both of the parity and the disparity individuals showed similar results in that they adapted well and kept high FS as far as tested by 4,000 generations (Figures 4A,C). At higher mutation rates, however, a clear difference was observed between the two models. In the disparity model, even when the mutation rate was as high as 8.0, the individuals showed high adaptability and kept a stable FS. Especially, an appropriate rate of crossover (0.2) increased the FS. In case of the higher crossover rate (2.0), FS was increased with fluctuations. However, the quick increase of the FS curve at early stages of the simulation may mean that the population will quickly occupy the niche, indicating that high crossover rates might act as an advantageous factor for evolution. Individuals with asexual production showed medial FS (Figure 4B). When the parity and the disparity individuals competed with each other in the same niche, the latter quickly drove the former away from the niche (data not shown; see Wada et al., 1993).


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

Furusawa M - Front Oncol (2012)

Results of the simulation with the “neo-Darwinian genetic algorithm” in the diploid and sexual world are shown.(A) Disparity individuals with mutation rate (n) = 0.1. Green, no crossover; blue, crossover frequency (CF) = 0.2/chromosome; red, CF = 2.0; and black, asexual and diploid. (B) Disparity individuals n = 8.0. Green, no crossover: blue, CF = 0.2; red, CF = 2.0; and black, asexual. (C) Parity individuals n = 0.1. Green, no crossover; blue, CF = 0.2; red, CF = 2.0; and black, asexual. (D) Parity individual with various mutation rates. Black, n = 2.0 without crossover; magenta, n = 2.32 without crossover; cyan, n = 2.32 and CF = 2.0; red, n = 2.4 without crossover; and blue, n = 2.4 and CF = 2.0. Adapted from Wada et al. (1993); Copyright 1993, National Academy of Sciences, USA.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 4: Results of the simulation with the “neo-Darwinian genetic algorithm” in the diploid and sexual world are shown.(A) Disparity individuals with mutation rate (n) = 0.1. Green, no crossover; blue, crossover frequency (CF) = 0.2/chromosome; red, CF = 2.0; and black, asexual and diploid. (B) Disparity individuals n = 8.0. Green, no crossover: blue, CF = 0.2; red, CF = 2.0; and black, asexual. (C) Parity individuals n = 0.1. Green, no crossover; blue, CF = 0.2; red, CF = 2.0; and black, asexual. (D) Parity individual with various mutation rates. Black, n = 2.0 without crossover; magenta, n = 2.32 without crossover; cyan, n = 2.32 and CF = 2.0; red, n = 2.4 without crossover; and blue, n = 2.4 and CF = 2.0. Adapted from Wada et al. (1993); Copyright 1993, National Academy of Sciences, USA.
Mentions: The results are representatively shown in Figure 4. At the low mutation rate (0.1), both of the parity and the disparity individuals showed similar results in that they adapted well and kept high FS as far as tested by 4,000 generations (Figures 4A,C). At higher mutation rates, however, a clear difference was observed between the two models. In the disparity model, even when the mutation rate was as high as 8.0, the individuals showed high adaptability and kept a stable FS. Especially, an appropriate rate of crossover (0.2) increased the FS. In case of the higher crossover rate (2.0), FS was increased with fluctuations. However, the quick increase of the FS curve at early stages of the simulation may mean that the population will quickly occupy the niche, indicating that high crossover rates might act as an advantageous factor for evolution. Individuals with asexual production showed medial FS (Figure 4B). When the parity and the disparity individuals competed with each other in the same niche, the latter quickly drove the former away from the niche (data not shown; see Wada et al., 1993).

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