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Environmental triggers may promote human genetic variation

FUKUOKA, Japan In this month's issue of the leading scientific journal Genome Research, scientists from Kyushu University report how environmentally damaged DNA may contribute to human genetic diversity. They describe the co-occurrence of an aberrant nucleobase, called 8-oxoguanine (8-oxoG), with genomic regions enriched in meiotic recombination "hotspots" and single nucleotide polymorphisms (SNPs). The findings have implications for understanding the interplay between heredity and the environment in shaping human phenotypic variation.

Human DNA is constantly barraged by a variety of environmental agents, including UV light and chemicals, as well as by reactive oxygen species (ROS), which are produced as byproducts of normal metabolic reactions or as molecular executors of host defense. These agents may cause the nucleobases in DNA to spontaneously undergo a chemical transformation known as oxidation. 8-oxoG is an oxidized form of the common nucleobase guanine (G), and when present in the genome, may form an unconventional base-pair with adenine (A). When DNA replication occurs, the abnormally placed adenine is paired with a thymine (T) instead of the original guanine, thereby resulting in a permanent nucleobase change.

One might intuitively expect the distribution of aberrant 8-oxoG nucleobases to be randomly distributed throughout the genome, but in their new study, Dr. Yusaku Nakabeppu and his colleagues demonstrated otherwise. Nakabeppu teamed up with Drs. Mizuki Ohno and Tomofumi Miura, among others, to investigate the distribution of 8-oxoG on spreads of normal human chromosomes with fluorescently labeled antibodies that specifically attached to 8-oxoG positions. Intriguingly, the dot-like fluorescent signals did not cover the chromosomes uniformly but rather, exhibited a striking bias for chromosomal regions that contain higher meiotic recombination rates and SNP densities. Furthermore, the distribution and intensity of 8-
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Contact: Maria Smit
smit@cshl.edu
516-422-4013
Cold Spring Harbor Laboratory
30-Apr-2006


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