SGER: Reducing the Rates of Oxidation of Essential Domains of Genomes

University Of Texas At Austin, Austin TX

Investigators

Abstract

This exploratory research project will statistically analyze databases containing the nucleotide sequences of genomes of different species to define the boundaries of their genes' exons, introns and intergene domains to determine (a) whether the oxidation rates of essential domains of the genomes are reduced by making these noble through exclusion of rapidly oxidized nucleotide sequences, and (b) whether the essential domains are cathodically protected by rapidly oxidized sequences in nearby non-essential domains. The species will be ranked by the relative survival value of the reduction of the oxidation rate of their essential domains, the value increasing with the time required for their species to reproduce, and with the inverse of the number of offspring per generation. The aim is to test the hypothesis that the essential domains are ennobled when the survival value is low but are cathodically protected when it is high. Certain precursors are generated in living cells and react to form strong oxidizing agents at residual concentrations high enough to produce many oxidative lesions in the DNA of every cell. Although DNA repair enzymes continuously recognize, excise and repair these lesions, there are many oxidative genome lesions in every cell, causing aging and mutations. Just as the corrosion rate of an alloy depends on its constituent metals, the oxidation rate of DNA depends on its nucleotide composition. Reducing the oxidation rates of those DNA segments that code for proteins and control protein production should be critical to the survival of species. The proposed exploratory research will test the hypothesis that the degree and complexity of oxidation protection increases with its value for the survival of the species. Ultimately, avoiding oxidation of essential DNA sequences of genomes is important in reducing human aging and cancer.