Environmental triggers may promote human genetic variation

oxoG was remarkably similar in different individuals.

"We suggest that 8-oxoG accumulation in a particular region of a chromosome causes meiotic recombination," says Nakabeppu. "Our theory is supported by studies showing that enzymes involved in the repair of oxidative DNA damage can also induce homologous recombination. These enzymes are highly expressed in the ovary and testis, where meiotic recombination normally occurs. Furthermore, meiotic recombination rates in females are significantly higher than in males, probably because oocytes are exposed to oxidative stress for longer periods of time than are spermatocytes."

The uneven distribution of SNPs across the human genome has been documented for some time, but the causes of these nucleobase substitutions and the factors determining their distribution are largely unknown. Nakabeppu, therefore, also suggests that 8-oxoG, due to its mutagenic potential, may contribute to the formation of SNPs.

But why the clustering of 8-oxoG?

"The factors determining the distribution of 8-oxoG are still unknown," explains Nakabeppu. "One can certainly argue that there must be another factor that coincidentally increases the recombination rate or the formation of SNPs in addition to the accumulation of 8-oxoG in a particular region of the chromosome. The local structures of chromosomes and their replication or transcription might help to determine the distribution of 8-oxoG, but further analysis is required to fully understand the mechanistic relationship between 8-oxoG, recombination, and mutagenesis."


Contact: Maria Smit
Cold Spring Harbor Laboratory

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