Oxidative Stress Causes Large Number of Genetic Mutations
PNAS paper details study with C. elegans that also showed that junk DNA is affected by natural selection.!--h2>
Oxidative DNA damage is a primary cause of gene mutations, according to a team of invistigators. They tracked genetic mutations in C. elegans over 250 generations, which they say is the human equivalent of about 5,000. Additionally, the group found that natural selection also affects junk DNA, parts of the genome that don't contain genes.
The results are published in the Proceedings of the National Academy of Sciences. The analysis was done by scientists at Oregon State University (OSU), Indiana University, University of Florida, and University of New Hampshire.
Oxidative stress has been suspected as a mechanism for some of the processes that lead to aging and disease. This is one of the first studies that clearly demonstrates the effects of oxidative damage at a genome-wide scale, points out Dee Denver, an assistant professor of zoology at OSU and principal investigator.
“The research showed that the majority of all DNA mutations bear the signature of oxidative stress,” Denver notes. “That's exactly what you would expect if you believe that oxidative stress is an underlying cause of aging and disease.”
During the research, C. elegans accumulated 391 genetic mutations through normal life processes. That's more than 10 times as many mutations as have ever been tracked in a study such as this, according to the team.
“Genetic mutations in animals are actually pretty rare; they don't happen very often unless they are induced by something,” Denver explains. “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."
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. Guanine is known to be particularly sensitive to oxidative damage.
The research also found that mutation and natural selection are operating in the junk DNA parts of the roundworm, which actually comprise about 75% of its genome but traditionally were not thought to play any major role in life and genetic processes. This suggests that these poorly understood parts of the genome may have important biological roles that are not yet known.