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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 linear DNA is shown. A broad arrow indicates a template DNA strand, a thin arrow indicates a newly synthesized leading strand and a dashed thin arrow indicates a newly synthesized lagging strand. The black circle with a short bar crossing strands indicates a point mutation. Each number on the side of a black circle indicates a base substitution at a different site. The ori indicates the replication origin. Two mutations per a single replication are introduced exclusively in the lagging strand. Notice that for instance, in the family line of the genomes with the symbol mark (✪), the genotype is guaranteed forever.
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Figure 1: The distribution of mutations according to the deterministic disparity model of a linear DNA is shown. A broad arrow indicates a template DNA strand, a thin arrow indicates a newly synthesized leading strand and a dashed thin arrow indicates a newly synthesized lagging strand. The black circle with a short bar crossing strands indicates a point mutation. Each number on the side of a black circle indicates a base substitution at a different site. The ori indicates the replication origin. Two mutations per a single replication are introduced exclusively in the lagging strand. Notice that for instance, in the family line of the genomes with the symbol mark (✪), the genotype is guaranteed forever.

Mentions: Figure 1 shows a pedigree of a linear chromosomal DNA with a single ori at its upper end, i.e., corresponding to a single replicore in higher organisms. It is roughly estimated that several genes, on average, exist in a single replicore. According to our disparity model, biased mutations occur in the lagging strand (Furusawa and Doi, 1992, 1998). The pedigree by the deterministic illustration implies several interesting features; (1) the ancestor has been kept forever; (2) a genotype that once appeared in the past, has been precisely guaranteed in any generation; (3) the threshold of mutation rates is increased (actually, the threshold disappears in this model); (4) even if circumstances changed dramatically, the fittest individual will be selected as a new ancestor and start again to produce a new pedigree as well (Figure 1). These outstanding features appear to be beneficial for evolution.


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 linear DNA is shown. A broad arrow indicates a template DNA strand, a thin arrow indicates a newly synthesized leading strand and a dashed thin arrow indicates a newly synthesized lagging strand. The black circle with a short bar crossing strands indicates a point mutation. Each number on the side of a black circle indicates a base substitution at a different site. The ori indicates the replication origin. Two mutations per a single replication are introduced exclusively in the lagging strand. Notice that for instance, in the family line of the genomes with the symbol mark (✪), the genotype 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 1: The distribution of mutations according to the deterministic disparity model of a linear DNA is shown. A broad arrow indicates a template DNA strand, a thin arrow indicates a newly synthesized leading strand and a dashed thin arrow indicates a newly synthesized lagging strand. The black circle with a short bar crossing strands indicates a point mutation. Each number on the side of a black circle indicates a base substitution at a different site. The ori indicates the replication origin. Two mutations per a single replication are introduced exclusively in the lagging strand. Notice that for instance, in the family line of the genomes with the symbol mark (✪), the genotype is guaranteed forever.
Mentions: Figure 1 shows a pedigree of a linear chromosomal DNA with a single ori at its upper end, i.e., corresponding to a single replicore in higher organisms. It is roughly estimated that several genes, on average, exist in a single replicore. According to our disparity model, biased mutations occur in the lagging strand (Furusawa and Doi, 1992, 1998). The pedigree by the deterministic illustration implies several interesting features; (1) the ancestor has been kept forever; (2) a genotype that once appeared in the past, has been precisely guaranteed in any generation; (3) the threshold of mutation rates is increased (actually, the threshold disappears in this model); (4) even if circumstances changed dramatically, the fittest individual will be selected as a new ancestor and start again to produce a new pedigree as well (Figure 1). These outstanding features appear to be beneficial for evolution.

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