Comprehensive fitness maps of Hsp90 show widespread environmental dependence
Comprehensive fitness maps of Hsp90 show widespread environmental dependence
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DOI：
10.7554/elife.53810
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发表时间：
2020-03-04
期刊：
影响因子：
7.7
通讯作者：
Bolon, Daniel N. A.
中科院分区：
文献类型：
--
作者：
Flynn, Julia M.;Rossouw, Ammeret;Bolon, Daniel N. A.
基因与环境的相互作用长期以来一直被认为是影响分子进化的理论。然而，大多数突变的环境依赖性仍然未知。使用深度突变扫描，我们对酵母进行了改造，使其具有编码Hsp 90中14，160个氨基酸变体的所有44，604个单密码子变化，并量化了标准条件和五种应激条件下的生长影响。据我们所知，这些是最大的确定的点突变体的综合适应度图。许多变体的生长在不同条件下不同，表明环境对Hsp 90进化有很大影响。多种变体在个别条件下提供生长优势;然而，这些变体在其他环境中往往表现出生长缺陷。在现存真核生物中观察到的Hsp 90序列的多样性优先包含在所有测试条件下支持稳健生长的变体。而不是有利于在个别条件下的替代，热休克蛋白90的长期选择性压力可能是波动的环境，导致在各种条件下的鲁棒性。
Gene-environment interactions have long been theorized to influence molecular evolution. However, the environmental dependence of most mutations remains unknown. Using deep mutational scanning, we engineered yeast with all 44,604 single codon changes encoding 14,160 amino acid variants in Hsp90 and quantified growth effects under standard conditions and under five stress conditions. To our knowledge, these are the largest determined comprehensive fitness maps of point mutants. The growth of many variants differed between conditions, indicating that environment can have a large impact on Hsp90 evolution. Multiple variants provided growth advantages under individual conditions; however, these variants tended to exhibit growth defects in other environments. The diversity of Hsp90 sequences observed in extant eukaryotes preferentially contains variants that supported robust growth under all tested conditions. Rather than favoring substitutions in individual conditions, the long-term selective pressure on Hsp90 may have been that of fluctuating environments, leading to robustness under a variety of conditions.