Dunham Maitreya J, Badrane Hassan, Ferea Tracy, Adams Julian, Brown Patrick O, Rosenzweig Frank, Botstein David
Department of Genetics, and Howard Hughes Medical Institute and Department of Biochemistry, Stanford University Medical School, Stanford, CA 94305, USA.
Proc Natl Acad Sci U S A. 2002 Dec 10;99(25):16144-9. doi: 10.1073/pnas.242624799. Epub 2002 Nov 21.
Genome rearrangements, especially amplifications and deletions, have regularly been observed as responses to sustained application of the same strong selective pressure in microbial populations growing in continuous culture. We studied eight strains of budding yeast (Saccharomyces cerevisiae) isolated after 100-500 generations of growth in glucose-limited chemostats. Changes in DNA copy number were assessed at single-gene resolution by using DNA microarray-based comparative genomic hybridization. Six of these evolved strains were aneuploid as the result of gross chromosomal rearrangements. Most of the aneuploid regions were the result of translocations, including three instances of a shared breakpoint on chromosome 14 immediately adjacent to CIT1, which encodes the citrate synthase that performs a key regulated step in the tricarboxylic acid cycle. Three strains had amplifications in a region of chromosome 4 that includes the high-affinity hexose transporters; one of these also had the aforementioned chromosome 14 break. Three strains had extensive overlapping deletions of the right arm of chromosome 15. Further analysis showed that each of these genome rearrangements was bounded by transposon-related sequences at the breakpoints. The observation of repeated, independent, but nevertheless very similar, chromosomal rearrangements in response to persistent selection of growing cells parallels the genome rearrangements that characteristically accompany tumor progression.
在连续培养的微生物群体中，基因组重排，尤其是扩增和缺失，经常被观察到是对持续施加相同强选择压力的反应。我们研究了在葡萄糖限制的恒化器中生长100 - 500代后分离出的8株芽殖酵母（酿酒酵母）。通过基于DNA微阵列的比较基因组杂交，以单基因分辨率评估DNA拷贝数的变化。这些进化菌株中有6株由于染色体的大规模重排而成为非整倍体。大多数非整倍体区域是易位的结果，包括在14号染色体上紧邻CIT1的一个共享断点的三个实例，CIT1编码在三羧酸循环中执行关键调控步骤的柠檬酸合酶。三株菌株在4号染色体的一个区域有扩增，该区域包括高亲和力己糖转运蛋白；其中一株还具有上述14号染色体的断裂。三株菌株在15号染色体右臂有广泛的重叠缺失。进一步分析表明，这些基因组重排中的每一个在断点处都由转座子相关序列界定。在生长细胞的持续选择下观察到重复、独立但非常相似的染色体重排，这与肿瘤进展中典型伴随的基因组重排相似。
