Promotion of Evolution by Intracellular Coexistence of Mutator and Normal DNA Polymerases

Aoki, Kazuhiro; Furusawa, Mitsuru

doi:10.1006/jtbi.2000.2257

Cited by 8 publications

(11 citation statements)

References 42 publications

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“…Using a “hill-climbing” game, we showed that the intracellular coexistence of error-prone mutator DNA polymerase and normal high fidelity DNA polymerase increased the mutation threshold and accelerated evolution (Aoki and Furusawa, 2001 ).…”

Section: Acceleration Of Evolution Using Digital Organisms With Dispamentioning

confidence: 99%

The disparity mutagenesis model predicts rescue of living things from catastrophic errors

Furusawa¹

2014

Front. Genet.

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In animals including humans, mutation rates per generation exceed a perceived threshold, and excess mutations increase genetic load. Despite this, animals have survived without extinction. This is a perplexing problem for animal and human genetics, arising at the end of the last century, and to date still does not have a fully satisfactory explanation. Shortly after we proposed the disparity theory of evolution in 1992, the disparity mutagenesis model was proposed, which forms the basis for an explanation for an acceleration of evolution and species survival. This model predicts a significant increase of the mutation threshold values if the fidelity difference in replication between the lagging and leading strands is high enough. When applied to biological evolution, the model predicts that living things, including humans, might overcome the lethal effect of accumulated deleterious mutations and be able to survive. Artificially derived mutator strains of microorganisms, in which an enhanced lagging-strand-biased mutagenesis was introduced, showed unexpectedly high adaptability to severe environments. The implications of the striking behaviors shown by these disparity mutators will be discussed in relation to how living things with high mutation rates can avoid the self-defeating risk of excess mutations.

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Section: Acceleration Of Evolution Using Digital Organisms With Dispamentioning

confidence: 99%

The disparity mutagenesis model predicts rescue of living things from catastrophic errors

Furusawa¹

2014

Front. Genet.

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“…The authenticity of our disparity model of evolution has been verified theoretically and experimentally. It was shown that co-existence of normal and error-prone RNA polymerase gave rise to the increase or the disappearance of error threshold in the Eigen-Schuster’s quasi-species [ 10 ], and that in the evolution games, the disparity model well overwhelmed the conventional “parity mutagenesis model”, in which the fidelity difference between the lagging and leading strand were out of consideration [ 11 , 12 ]. Moreover, using living microorganisms such as E. coli , yeasts and malaria parasites, we reported that the “disparity mutator” performing lagging-strand-biased-mutagenesis significantly promoted adaptive evolution [5] .…”

Section: Introductionmentioning

confidence: 99%

“…Thus, we decided to use computer simulations to estimate what actually happens in a mutator’s cell body. We have used so far a very simple GA which consists of a double-stranded structure with a linear arrangement of bits, and each bit corresponds to an individual gene [ 11 , 12 ].…”

Section: Introductionmentioning

confidence: 99%

Disparity mutagenesis model possesses the ability to realize both stable and rapid evolution in response to changing environments without altering mutation rates.

Fujihara

Furusawa²

2016

Heliyon

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It has been shown that the disparity model, in which mutations are introduced exclusively in the lagging strand, has a great advantage in the promotion of evolution, compared with the conventional parity mutagenesis model. To understand much more about the characteristic of the disparity model, a novel 2-D genetic algorithm (GA) which reflected gene interactions was developed. The GA consisting of the lattice model showed powerful abilities to evolve. Even under conditions of high mutation rates with an extra genetic load, the GA could quickly evolve and finally attain a long stable state with high fitness scores.Arbitrary interruption of the stable state of evolution by various lengths of environmental stress could produce new individuals with different genotypes within relatively short periods and the mutants finally occupy the population; that brought back the picture of “punctuated equilibrium”. Interestingly, this phenomenon could be reproduced with certainty without changing mutation rates at all.As long as the fidelity difference between the lagging and leading strand was kept high enough, the robustness of the disparity model was very high. The acceleration or slowdown of evolution can be unambiguously introduced only by environmental changes, and the seesawing mutation rate is not the necessary condition for changing the speed of evolution.

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“…To obtain genetic diversity, an errorprone DNA polymerase technique is employed. Thus, a mutation is inserted into DNA polymerase  which is responsible for synthesis of the lagging strands, such that the polymerase loses its DNA repair function (Aoki and Furusawa 2001).…”

Section: Introductionmentioning

confidence: 99%

The improvement of riboflavin production in Ashbya gossypii via disparity mutagenesis and DNA microarray analysis

Park

Itō

Nariyama

et al. 2011

Appl Microbiol Biotechnol

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We generated a high riboflavin-producing mutant strain of Ashbya gossypii by disparity mutagenesis using mutation of DNA polymerase δ in the lagging strand, resulting in loss of DNA repair function by the polymerase. Among 1,353 colonies generated in the first screen, 26 mutants produced more than 3 g/L of riboflavin. By the second screen and single-colony isolation, nine strains that produced more than 5.2 g/L of riboflavin were selected as high riboflavin-producing strains. These mutants were resistant to oxalic acid and hydrogen peroxide as antimetabolites. One strain (W122032) produced 13.7 g/L of riboflavin in a 3-L fermentor using an optimized medium. This represents a ninefold improvement on the production of the wild-type strain. Proteomic analysis revealed that ADE1, RIB1, and RIB5 proteins were expressed at twofold higher levels in this strain than in the wild type. DNA microarray analysis showed that purine and riboflavin biosynthetic pathways were upregulated, while pathways related to carbon source assimilation, energy generation, and glycolysis were downregulated. Genes in the riboflavin biosynthetic pathway were significantly overexpressed during both riboflavin production and stationary phases, for example, RIB1 and RIB3 were expressed at greater than sixfold higher levels in this strain compared to the wild type. These results indicate that the improved riboflavin production in this strain is related to a shift in carbon flux from β-oxidation to the riboflavin biosynthetic pathway.

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Promotion of Evolution by Intracellular Coexistence of Mutator and Normal DNA Polymerases

Cited by 8 publications

References 42 publications

The disparity mutagenesis model predicts rescue of living things from catastrophic errors

The disparity mutagenesis model predicts rescue of living things from catastrophic errors

Disparity mutagenesis model possesses the ability to realize both stable and rapid evolution in response to changing environments without altering mutation rates.

The improvement of riboflavin production in Ashbya gossypii via disparity mutagenesis and DNA microarray analysis

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