Wirgin I I, D'Amore M, Grunwald C, Goldman A, Garte S J
Institute of Environmental Medicine, New York University Medical Center, New York 10016.
Biochem Genet. 1990 Oct;28(9-10):459-75. doi: 10.1007/BF00554374.
It has been reported that Atlantic tomcod (Microgadus tomcod) from the Hudson River exhibit an extremely high incidence of liver tumors. More than 90% of spawning 2-year-old fish display hepatocellular carcinomas. In contrast, representatives of this species from a relatively pristine environment show a much lower incidence of tumors. Genomic DNA and mitochondrial DNA (mtDNA) were isolated from tomcod from the Hudson River, New York, and the Saco River and Royal River, Maine. We found a statistically significant difference in the frequency of PstI-generated restriction fragment length polymorphisms in the abl cellular oncogene between Hudson and Maine tomcod. Allelic variation was observed at two of the three abl domains scored. A single composite genotype seen in approximately 40% of Hudson River fish was seen in only one Maine fish. This polymorphism enabled us to differentiate a Hudson River population from that encountered in the Maine rivers. This is the first demonstration of a population-specific polymorphism at a cellular oncogene locus in any species. In contrast, no restriction site polymorphisms were seen in mtDNA between the populations. The lack of mtDNA diversity in these fish is consistent with the geological history of the area. In combination, these results suggest that the genetic diversity observed at the c-abl oncogene locus must have been a fairly recent event and that oncogene loci may be particularly sensitive to mutational change.
据报道,来自哈得逊河的大西洋小鳕(Microgadus tomcod)肝脏肿瘤发病率极高。超过90%的两岁产卵期鱼类患有肝细胞癌。相比之下,来自相对原始环境的该物种代表肿瘤发病率要低得多。从纽约哈得逊河、缅因州萨科河和皇家河的小鳕中分离出基因组DNA和线粒体DNA(mtDNA)。我们发现,哈得逊河小鳕和缅因州小鳕之间,abl细胞癌基因中由PstI产生的限制性片段长度多态性频率存在统计学上的显著差异。在所分析的abl三个结构域中的两个结构域观察到了等位基因变异。在大约40%的哈得逊河鱼类中出现的单一复合基因型,在缅因州的鱼类中仅在一条鱼中出现。这种多态性使我们能够区分哈得逊河种群和缅因州河流中的种群。这是在任何物种的细胞癌基因位点首次证明种群特异性多态性。相比之下,种群之间的mtDNA未观察到限制性位点多态性。这些鱼类中mtDNA缺乏多样性与该地区的地质历史一致。综合来看,这些结果表明,在c-abl癌基因位点观察到的遗传多样性一定是相当近期的事件,并且癌基因位点可能对突变变化特别敏感。