Study Finds Oxidative Stress a Primary Cause of Genetic Mutations

 Study Finds Oxidative Stress a Primary Cause of Genetic Mutations
American scientists have shown for the first time that oxidative DNA damage is a primary cause of the process of mutation, which is the main cause for evolution and also a leading cause of aging, cancer and other diseases.
The analysis done by scientists from Oregon State University, Indiana University, the University of Florida and University of New Hampshire also suggests that natural selection is affecting the parts of the genome that don't contain genes - supposedly "junk" DNA that increasingly appears to have important roles in life processes that are very poorly understood.

Published in Proceedings of the National Academy of Sciences, this research is said to be unusual because the model animal used for the study, a type of roundworm called C. elegans, was tracked through 250 generations.

In that period of time, the roundworm accumulated 391 genetic mutations through normal life processes, more than 10 times as many mutations as have ever before been tracked in a study such as this.

Despite their vast evolutionary separation as life forms, this tiny roundworm and humans still share comparable forms of DNA maintenance.

"Genetic mutations in animals are actually pretty rare, they don't happen very often unless they are induced by something. The value of using this roundworm is that it reaches reproductive age in about four days, so we can study changes that happen through hundreds of generations, using advanced genome sequencing technology," said Dee Denver, an assistant professor of zoology at OSU and principal investigator on the study.

Genetic mutations are a fundamental part of the biological process of life and the basis of evolution.

A primary finding of the new study is that a predominant number of genetic mutations are linked to guanine, one of the four basic nucleotides that make up DNA and form the genetic code of life.

Guanine is known to be particularly sensitive to oxidative damage, according to background information in the research article.

"Most life on Earth depends in some form on oxygen, which is great at the production of energy. But we pay a high price for our dependence on oxygen, because the process of using it is not 100 percent efficient, and it can result in free oxygen radicals that can damage proteins, fats and DNA. And this process gets worse with age, as free radicals accumulate and begin to cause disease," Denver said.

The researcher claimed it to be one of the first studies to clearly show the effects of oxidative damage at a genome-wide scale.

"The research showed that the majority of all DNA mutations bear the signature of oxidative stress. That's exactly what you would expect if you believe that oxidative stress is an underlying cause of aging and disease," Denver said.

The study has also shown that mutation and natural selection is also operating in the "junk DNA" parts of the roundworm, which actually comprises about 75 percent of its genome but traditionally was not thought to play any major role in life and genetic processes.

Based on this finding, Denver says that these poorly-understood and little appreciated parts of the genome may have important biological roles that are not yet known.

Oxidative stress for decades has been suspected as a mechanism for some of the processes that lead to aging and disease, and it has been studied extensively for that reason.

This research provides a better fundamental understanding of the genetic impacts of oxidative stress and its role in both genetic disease and evolution, the researchers say.


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