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

Mitsuru Furusawa

doi:10.3389/fgene.2014.00421

Abstract

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.

Highlights

The number of mutations per generation per diploid was calculated for several species, and found to range widely: nematode (0.32), drosophila (2.8), mouse (60), and human (128) (Drake et al, 1998)
ACCELERATION OF EVOLUTION USING DIGITAL ORGANISMS WITH DISPARITY MUTAGENESIS 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)
The following conclusions can be deduced from experiments using disparity-mutators of living organisms: (1) Growth rates of disparity mutators and of the intact cells are nearly equal, when cultured in normal conditions. This feature would be an essential condition for evolution experiments, because a delayed cell-cycle will work against the rate of accumulating mutations, resulting in delayed adaptive evolution; (2) The principle of the disparity mutagenesis model may be applicable to all living prokaryotes and eukaryotes; (3) A prolonged period of high mutation rates, during which most likely average mutation rates exceed the threshold value, does not necessarily lead to the death of organisms; (4) To attain a final intended phenotype, a number of appropriate mutations should be introduced in a correct order (Furusawa, 2013) and most probably, genomewide changes with mutations are necessary

Summary

Mitsuru Furusawa*

Reviewed by: Xianyun Mao, Guardian Analytics, USA David Goode, Peter MacCallum Cancer Centre, Australia Kun Chen, Dana-Farber Cancer Institute, USA. Mutation rates per generation exceed a perceived threshold, and excess mutations increase genetic load. 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.

Findings

INTRODUCTION

DISCUSSION