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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 mutations according to the deterministic disparity model of a circular genome is shown. The ori is replication origin. DNA synthesis starts from the ori to opposite directions (short arrows). term, the position where the progress of DNA synthesis meets. (a) and (b), The left and right hemispheres of the genome, respectively. Broad circle indicates the template strand, and thin circle the newly synthesized strand. The thin circle with small arrow heads is the lagging strand. The black circle with a short bar crossing strands is a point mutation. Each number followed by a or b indicates a base substitution at different sites. Two biased mutations are introduced in the lagging strand in every replication. Notice that for instance, in the family line of the genomes with the symbol mark (✪), the genotype of the left hemisphere is guaranteed forever.
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Figure 6: The distribution of mutations according to the deterministic disparity model of a circular genome is shown. The ori is replication origin. DNA synthesis starts from the ori to opposite directions (short arrows). term, the position where the progress of DNA synthesis meets. (a) and (b), The left and right hemispheres of the genome, respectively. Broad circle indicates the template strand, and thin circle the newly synthesized strand. The thin circle with small arrow heads is the lagging strand. The black circle with a short bar crossing strands is a point mutation. Each number followed by a or b indicates a base substitution at different sites. Two biased mutations are introduced in the lagging strand in every replication. Notice that for instance, in the family line of the genomes with the symbol mark (✪), the genotype of the left hemisphere is guaranteed forever.

Mentions: Figure 6 shows the deterministic illustrations of the genotypes in the pedigree of the disparity-mutator of bacteria with a single circular genomic DNA. The presence of a given genotype that has once appeared in the left or right hemisphere of the genome is guaranteed forever. Accordingly, at the left or the right hemisphere of the circular genome, the same phenomenon as shown in the pedigree of the disparity model with a liner DNA can be expected (Figure 1). This might explain the reason why the dnaQ49 mutator showed such a high adaptability against different antibiotics.


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 mutations according to the deterministic disparity model of a circular genome is shown. The ori is replication origin. DNA synthesis starts from the ori to opposite directions (short arrows). term, the position where the progress of DNA synthesis meets. (a) and (b), The left and right hemispheres of the genome, respectively. Broad circle indicates the template strand, and thin circle the newly synthesized strand. The thin circle with small arrow heads is the lagging strand. The black circle with a short bar crossing strands is a point mutation. Each number followed by a or b indicates a base substitution at different sites. Two biased mutations are introduced in the lagging strand in every replication. Notice that for instance, in the family line of the genomes with the symbol mark (✪), the genotype of the left hemisphere is guaranteed forever.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 6: The distribution of mutations according to the deterministic disparity model of a circular genome is shown. The ori is replication origin. DNA synthesis starts from the ori to opposite directions (short arrows). term, the position where the progress of DNA synthesis meets. (a) and (b), The left and right hemispheres of the genome, respectively. Broad circle indicates the template strand, and thin circle the newly synthesized strand. The thin circle with small arrow heads is the lagging strand. The black circle with a short bar crossing strands is a point mutation. Each number followed by a or b indicates a base substitution at different sites. Two biased mutations are introduced in the lagging strand in every replication. Notice that for instance, in the family line of the genomes with the symbol mark (✪), the genotype of the left hemisphere is guaranteed forever.
Mentions: Figure 6 shows the deterministic illustrations of the genotypes in the pedigree of the disparity-mutator of bacteria with a single circular genomic DNA. The presence of a given genotype that has once appeared in the left or right hemisphere of the genome is guaranteed forever. Accordingly, at the left or the right hemisphere of the circular genome, the same phenomenon as shown in the pedigree of the disparity model with a liner DNA can be expected (Figure 1). This might explain the reason why the dnaQ49 mutator showed such a high adaptability against different antibiotics.

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