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Karyotype engineering by chromosome fusion leads to reproductive isolation in yeast

机译：通过染色体融合进行核型设计导致酵母中的生殖分离

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Extant species have wildly different numbers of chromosomes, even among taxa with relatively similar genome sizes (for example, insects)(1,2). This is likely to reflect accidents of genome history, such as telomere-telomere fusions and genome duplication events(3-5). Humans have 23 pairs of chromosomes, whereas other apes have 24. One human chromosome is a fusion product of the ancestral state(6). This raises the question: how well can species tolerate a change in chromosome numbers without substantial changes to genome content? Many tools are used in chromosome engineering in Saccharomyces cerevisiae(7-10), but CRISPR-Cas9-mediated genome editing facilitates the most aggressive engineering strategies. Here we successfully fused yeast chromosomes using CRISPR-Cas9, generating a near-isogenic series of strains with progressively fewer chromosomes ranging from sixteen to two. A strain carrying only two chromosomes of about six megabases each exhibited modest transcriptomic changes and grew without major defects. When we crossed a sixteen-chromosome strain with strains with fewer chromosomes, we noted two trends. As the number of chromosomes dropped below sixteen, spore viability decreased markedly, reaching less than 10% for twelve chromosomes. As the number of chromosomes decreased further, yeast sporulation was arrested: a cross between a sixteen-chromosome strain and an eight-chromosome strain showed greatly reduced full tetrad formation and less than 1% sporulation, from which no viable spores could be recovered. However, homotypic crosses between pairs of strains with eight, four or two chromosomes produced excellent sporulation and spore viability. These results indicate that eight chromosome-chromosome fusion events suffice to isolate strains reproductively. Overall, budding yeast tolerates a reduction in chromosome number unexpectedly well, providing a striking example of the robustness of genomes to change.
机译：即使在具有相对相似的基因组大小的类群中，现存物种的染色体数目也大不相同（例如昆虫）（1,2）。这很可能反映了基因组历史的偶然性，例如端粒-端粒融合和基因组复制事件（3-5）。人类有23对染色体，而其他猿有24对。一条人类染色体是祖先状态的融合产物（6）。这就提出了一个问题：在不大幅改变基因组含量的情况下，物种对染色体数目变化的耐受程度如何？酿酒酵母（7-10）的染色体工程中使用了许多工具，但是CRISPR-Cas9介导的基因组编辑促进了最具攻击性的工程策略。在这里，我们成功地使用CRISPR-Cas9融合了酵母染色体，产生了一系列接近等基因的菌株，其染色体数目从16个减少到2个。一株仅携带两个大约六个兆碱基的染色体的菌株显示出适度的转录组变化，并且生长时没有重大缺陷。当我们将16染色体菌株与染色体较少的菌株杂交时，我们注意到了两个趋势。当染色体数目降至16条以下时，孢子活力显着下降，十二条染色体的孢子存活率不到10％。随着染色体数目的进一步减少，酵母的孢子形成被阻止：十六个染色体菌株和一个八个染色体菌株之间的杂交显示完全四分体的形成大大减少，孢子形成少于1％，因此无法回收活孢子。然而，具有八个，四个或两个染色体的成对菌株之间的同型杂交产生了优异的孢子形成和孢子活力。这些结果表明八个染色体-染色体融合事件足以生殖分离菌株。总体而言，出芽的酵母出人意料地很好地忍受了染色体数目的减少，为改变基因组的鲁棒性提供了一个引人注目的例子。

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  • 来源
    《Nature》 |2018年第7718期|392-396|共5页
  • 作者

    Luo Jingchuan; Sun Xiaoji; Cormack Brendan P.; Boeke Jef D.;

  • 作者单位

    NYU, Langone Hlth, Inst Syst Genet, New York, NY 10016 USA;

    NYU, Langone Hlth, Inst Syst Genet, New York, NY 10016 USA;

    Johns Hopkins Univ, Sch Med, Dept Mol Biol & Genet, Baltimore, MD 21205 USA;

    NYU, Langone Hlth, Inst Syst Genet, New York, NY 10016 USA;

  • 收录信息 美国《科学引文索引》(SCI);美国《工程索引》(EI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
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