Thierry Agnès, Khanna Varun, Créno Sophie, Lafontaine Ingrid, Ma Laurence, Bouchier Christiane, Dujon Bernard
Institut Pasteur, Unité de Génétique moléculaire des levures, CNRS UMR3525, Sorbonne Universités, UPMC, Univ. Paris 06 UFR927, 25, rue du Docteur Roux, F-75724 Paris, France.
Institut Pasteur, Genomic platform, 28, rue du Docteur Roux, F-75724 Paris, France.
Nat Commun. 2015 Jan 30;6:6154. doi: 10.1038/ncomms7154.
Copy number variation of chromosomal segments is now recognized as a major source of genetic polymorphism within natural populations of eukaryotes, as well as a possible cause of genetic diseases in humans, including cancer, but its molecular bases remain incompletely understood. In the baker's yeast Saccharomyces cerevisiae, a variety of low-order amplifications (segmental duplications) were observed after adaptation to limiting environmental conditions or recovery from gene dosage imbalance, and interpreted in terms of replication-based mechanisms associated or not with homologous recombination. Here we show the emergence of novel high-order amplification structures, with corresponding overexpression of embedded genes, during evolution under favourable growth conditions of severely unfit yeast cells bearing genetically disabled genomes. Such events form massively extended chromosomes, which we propose to call macrotene, whose characteristics suggest the products of intrachromosomal rolling-circle type of replication structures, probably initiated by increased accidental template switches under important cellular stress conditions.
染色体片段的拷贝数变异如今被认为是真核生物自然种群中遗传多态性的主要来源，也是包括癌症在内的人类遗传疾病的一个可能成因，但其分子基础仍未被完全理解。在面包酵母酿酒酵母中，在适应有限环境条件或从基因剂量失衡中恢复后，观察到了多种低阶扩增（片段重复），并根据与同源重组相关或不相关的基于复制的机制进行了解释。在这里，我们展示了在具有遗传缺陷基因组的严重不适应酵母细胞在有利生长条件下进化过程中，新型高阶扩增结构的出现以及嵌入基因的相应过表达。此类事件形成了大量延伸的染色体，我们提议将其称为“巨线染色体”，其特征表明是染色体内部滚环式复制结构的产物，可能是在重要细胞应激条件下偶然模板转换增加引发的。
