Department of Genomes and Genetics, Institut Pasteur, CNRS UMR3525, F75724 Paris, France.
Genes (Basel). 2021 Oct 23;12(11):1678. doi: 10.3390/genes12111678.
Novel, large-scale structural mutations were previously discovered during the cultivation of engineered strains in which essential tRNA synthetase genes were replaced by their orthologs from the distantly related yeast . Among those were internal segmental amplifications forming giant chromosomes as well as complex segmental rearrangements associated with massive amplifications at an unselected short locus. The formation of such novel structures, whose stability is high enough to propagate over multiple generations, involved short repeated sequences dispersed in the genome (as expected), but also novel junctions between unrelated sequences likely triggered by accidental template switching within replication forks. Using the same evolutionary protocol, we now describe yet another type of major structural mutation in the yeast genome, the formation of neochromosomes, with functional centromeres and telomeres, made of extra copies of very long chromosomal segments ligated together in novel arrangements. The novel junctions occurred between short repeated sequences dispersed in the genome. They first resulted in the formation of an instable neochromosome present in a single copy in the diploid cells, followed by its replacement by a shorter, partially palindromic neochromosome present in two copies, whose stability eventually increased the chromosome number of the diploid strains harboring it.
先前在培养工程菌株的过程中发现了新型的大规模结构突变，其中必需的 tRNA 合成酶基因被来自远缘酵母的同源物所取代。这些突变包括形成巨型染色体的内部片段扩增，以及与未选择的短基因座大量扩增相关的复杂片段重排。这些新型结构的形成，其稳定性足以在多个世代中传播，涉及在基因组中分散的短重复序列（如预期的那样），但也涉及在复制叉内意外模板转换引发的不相关序列之间的新连接。使用相同的进化方案，我们现在描述了酵母基因组中另一种主要结构突变，即具有功能着丝粒和端粒的新染色体的形成，它由非常长的染色体片段的额外拷贝连接在一起形成新的排列。新的连接发生在基因组中分散的短重复序列之间。它们首先导致不稳定的新染色体的形成，该染色体在二倍体细胞中仅存在一个拷贝，随后被一个较短的、部分回文的新染色体取代，该染色体存在两个拷贝，其稳定性最终增加了携带它的二倍体菌株的染色体数。
