Microbiology Doctoral Training Program, University of Wisconsin-Madison, Madison, United States.
Great Lakes Bioenergy Research Center, University of Wisconsin-Madison, Madison, United States.
Elife. 2021 Aug 2;10:e70564. doi: 10.7554/eLife.70564.
Copy number variation through gene or chromosome amplification provides a route for rapid phenotypic variation and supports the long-term evolution of gene functions. Although the evolutionary importance of copy-number variation is known, little is understood about how genetic background influences its tolerance. Here, we measured fitness costs of over 4000 overexpressed genes in 15 strains representing different lineages, to explore natural variation in tolerating gene overexpression (OE). Strain-specific effects dominated the fitness costs of gene OE. We report global differences in the consequences of gene OE, independent of the amplified gene, as well as gene-specific effects that were dependent on the genetic background. Natural variation in the response to gene OE could be explained by several models, including strain-specific physiological differences, resource limitations, and regulatory sensitivities. This work provides new insight on how genetic background influences tolerance to gene amplification and the evolutionary trajectories accessible to different backgrounds.
通过基因或染色体扩增的拷贝数变异为快速表型变异提供了途径，并支持基因功能的长期进化。虽然已经知道了拷贝数变异的进化重要性，但对于遗传背景如何影响其耐受性知之甚少。在这里，我们测量了代表不同谱系的 15 个菌株中 4000 多个过表达基因的适合度代价，以探索基因过表达（OE）耐受的自然变异。菌株特异性效应主导了基因 OE 的适合度代价。我们报告了与扩增基因无关的基因 OE 后果的全球差异，以及依赖于遗传背景的基因特异性效应。对基因 OE 反应的自然变异可以用几种模型来解释，包括菌株特异性的生理差异、资源限制和调控敏感性。这项工作提供了新的见解，说明遗传背景如何影响对基因扩增的耐受性以及不同背景下可获得的进化轨迹。
