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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

A “hill-climbing problem” is resolved using the parity and disparity “neo-Darwinian genetic algorithm.” The genome of the genetic algorithm consists of 16 bit and replicates using the leading and lagging strands. In parity models mutations are introduced evenly in both strands (A,B), while in disparity models biased mutations are introduced in the lagging strand (C,D). The vertical and horizontal axes are the fitness score and the distance of peaks from the starting position, respectively. Black dots symbolize the position of individuals at the end of the experiment. The larger the dots are, the more individuals have accumulated at specific positions. For details see text.
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Figure 3: A “hill-climbing problem” is resolved using the parity and disparity “neo-Darwinian genetic algorithm.” The genome of the genetic algorithm consists of 16 bit and replicates using the leading and lagging strands. In parity models mutations are introduced evenly in both strands (A,B), while in disparity models biased mutations are introduced in the lagging strand (C,D). The vertical and horizontal axes are the fitness score and the distance of peaks from the starting position, respectively. Black dots symbolize the position of individuals at the end of the experiment. The larger the dots are, the more individuals have accumulated at specific positions. For details see text.

Mentions: We constructed a GA, named neo-Darwinian algorithm, which consisted of the double-stranded genetic information like DNA (K. Aoki and M. Furusawa, unpublished). This GA replicates using the leading/lagging strands system. We compared the parity model with the disparity model. A simple “hill-climbing problem” with a rugged landscape was provided. The landscape was made using the gray code which has 686 peaks (Figure 3). An individual that has reached the foot of a given peak can go up the peak by adding a relatively small number of mutations, while a larger number of mutations are required when an individual moves to another peak at a longer distance.


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

Furusawa M - Front Oncol (2012)

A “hill-climbing problem” is resolved using the parity and disparity “neo-Darwinian genetic algorithm.” The genome of the genetic algorithm consists of 16 bit and replicates using the leading and lagging strands. In parity models mutations are introduced evenly in both strands (A,B), while in disparity models biased mutations are introduced in the lagging strand (C,D). The vertical and horizontal axes are the fitness score and the distance of peaks from the starting position, respectively. Black dots symbolize the position of individuals at the end of the experiment. The larger the dots are, the more individuals have accumulated at specific positions. For details see text.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 3: A “hill-climbing problem” is resolved using the parity and disparity “neo-Darwinian genetic algorithm.” The genome of the genetic algorithm consists of 16 bit and replicates using the leading and lagging strands. In parity models mutations are introduced evenly in both strands (A,B), while in disparity models biased mutations are introduced in the lagging strand (C,D). The vertical and horizontal axes are the fitness score and the distance of peaks from the starting position, respectively. Black dots symbolize the position of individuals at the end of the experiment. The larger the dots are, the more individuals have accumulated at specific positions. For details see text.
Mentions: We constructed a GA, named neo-Darwinian algorithm, which consisted of the double-stranded genetic information like DNA (K. Aoki and M. Furusawa, unpublished). This GA replicates using the leading/lagging strands system. We compared the parity model with the disparity model. A simple “hill-climbing problem” with a rugged landscape was provided. The landscape was made using the gray code which has 686 peaks (Figure 3). An individual that has reached the foot of a given peak can go up the peak by adding a relatively small number of mutations, while a larger number of mutations are required when an individual moves to another peak at a longer distance.

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