Epigenetic mutagenesis as program of age-related protein dysfunction and aging

Epigenetic mutagenesis as program of age-related protein dysfunction and aging DNA methylation plays an important polyfunctional role in ontogenesis of human and mammals. A steep rise in probability of mutational substitution of CpG dinucleotide by TpG dinucleotide in the genome is one of the consequences of DNA methylation. All spectrum (17) of possible DNA and protein mutations caused by CpG-dinucleotide methylation in DNA were characterized, and the three most dangerous mutations able to result in protein inactivation were isolated. The computer program that allows one to predict all most probable mutations in the analyzed gene and encoded protein was created. On the example of genes from humans and various mammals, it was demonstrated that the amount of potentially dangerous sites of epigenetic mutagenesis in exons was drastically decreased as a result of genome evolution. But, at the same time, unforced preservation of such sites and their persistence were established, indicating the occurrence of age-related protein dysfunction built into the genome epigenetic program, resulting in apoptosis and aging; this program is based on the set and position of methylated codons in exonic gene regions. It is assumed that the program of epigenetic mutagenesis limits the lifetime of an individual, accelerating the deliverance of the population from long-lived individuals that completed the reproductive period. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Russian Journal of Developmental Biology Springer Journals

Epigenetic mutagenesis as program of age-related protein dysfunction and aging

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Publisher
Springer Journals
Copyright
Copyright © 2015 by Pleiades Publishing, Inc.
Subject
Life Sciences; Developmental Biology; Animal Anatomy / Morphology / Histology
ISSN
1062-3604
eISSN
1608-3326
D.O.I.
10.1134/S106236041502006X
Publisher site
See Article on Publisher Site

Abstract

DNA methylation plays an important polyfunctional role in ontogenesis of human and mammals. A steep rise in probability of mutational substitution of CpG dinucleotide by TpG dinucleotide in the genome is one of the consequences of DNA methylation. All spectrum (17) of possible DNA and protein mutations caused by CpG-dinucleotide methylation in DNA were characterized, and the three most dangerous mutations able to result in protein inactivation were isolated. The computer program that allows one to predict all most probable mutations in the analyzed gene and encoded protein was created. On the example of genes from humans and various mammals, it was demonstrated that the amount of potentially dangerous sites of epigenetic mutagenesis in exons was drastically decreased as a result of genome evolution. But, at the same time, unforced preservation of such sites and their persistence were established, indicating the occurrence of age-related protein dysfunction built into the genome epigenetic program, resulting in apoptosis and aging; this program is based on the set and position of methylated codons in exonic gene regions. It is assumed that the program of epigenetic mutagenesis limits the lifetime of an individual, accelerating the deliverance of the population from long-lived individuals that completed the reproductive period.

Journal

Russian Journal of Developmental BiologySpringer Journals

Published: Mar 22, 2015

References

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