Ohno Mizuki, Miura Tomofumi, Furuichi Masato, Tominaga Yohei, Tsuchimoto Daisuke, Sakumi Kunihiko, Nakabeppu Yusaku
Division of Neurofunctional Genomics, Department of Immunobiology and Neuroscience, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan.
Genome Res. 2006 May;16(5):567-75. doi: 10.1101/gr.4769606.
8-Oxoguanine (8-oxoG), a major spontaneous form of oxidative DNA damage, is considered to be a natural cause of genomic diversity in organisms because of its mutagenic potential. The steady-state level of 8-oxoG in the nuclear genome of a human cell has been estimated to be several residues per 10(6) guanines. In the present study, to clarify the genome-wide distribution of 8-oxoG in the steady state, we performed fluorescence in situ detection of 8-oxoG on human metaphase chromosomes using a monoclonal antibody. Multiple dot-like signals were observed on each metaphase chromosome. We then mapped the position of the signal at megabase resolution referring to the cytogenetically identified chromosomal band, and demonstrated that 8-oxoG is unevenly distributed in the normal human genome and that the distribution pattern is conserved among different individuals. Moreover, we found that regions with a high frequency of recombination and single nucleotide polymorphisms (SNPs) are preferentially located within chromosomal regions with a high density of 8-oxoG. Our findings suggest that 8-oxoG is one of the main causes of frequent recombinations and SNPs in the human genome, which largely contribute to the genomic diversity in human beings.
8-氧代鸟嘌呤（8-oxoG）是氧化性DNA损伤的一种主要自发形式，因其具有诱变潜力，被认为是生物体基因组多样性的一个自然成因。据估计，人类细胞核基因组中8-氧代鸟嘌呤的稳态水平为每10⁶个鸟嘌呤中有几个残基。在本研究中，为了阐明稳态下8-氧代鸟嘌呤在全基因组中的分布情况，我们使用单克隆抗体对人类中期染色体上的8-氧代鸟嘌呤进行了荧光原位检测。在每条中期染色体上都观察到多个点状信号。然后，我们参照细胞遗传学鉴定的染色体带，以兆碱基分辨率绘制了信号位置图，结果表明8-氧代鸟嘌呤在正常人类基因组中分布不均，且这种分布模式在不同个体间是保守的。此外，我们发现重组和单核苷酸多态性（SNP）高频区域优先位于8-氧代鸟嘌呤高密度的染色体区域内。我们的研究结果表明，8-氧代鸟嘌呤是人类基因组中频繁重组和SNP的主要原因之一，这在很大程度上促成了人类的基因组多样性。
