The fitness landscape of a tRNA gene.
The fitness landscape of a tRNA gene.
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DOI：
10.1126/science.aae0568
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发表时间：
2016-05-13
期刊：
影响因子：
--
通讯作者：
Zhang J
中科院分区：
文献类型：
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作者：
Li C;Qian W;Maclean CJ;Zhang J
适应度景观描述了基因型-适应度关系，代表了进化轨迹的主要决定因素。然而，巨大的基因型空间，再加上难以测量的健身，阻碍了经验确定的健身景观。结合精确的基因替换和下一代测序，我们在高温挑战下量化了超过65，000种酵母菌株的达尔文适应性，每种酵母菌株都携带单拷贝的独特变体。 基因在其天然基因组位置。基因中大约1%的单点突变是有益的，而42%是有害的。几乎一半的突变对表现出显着的上位性，这有很强的负偏差，除了当突变发生在沃森-克里克配对位点。健身广泛相关的正确折叠的tRNA分子的预测分数，揭示了健身景观的生物物理基础。
Fitness landscapes describe the genotype-fitness relationship and represent major determinants of evolutionary trajectories. However, the vast genotype space, coupled with the difficulty of measuring fitness, has hindered the empirical determination of fitness landscapes. Combining precise gene replacement and next-generation sequencing, we quantify Darwinian fitness under a high-temperature challenge for over 65,000 yeast strains each carrying a unique variant of the single-copy gene at its native genomic location. Approximately 1% of single point mutations in the gene are beneficial, while 42% are deleterious. Almost half of all mutation pairs exhibit significant epistasis, which has a strong negative bias except when the mutations occur at Watson-Crick paired sites. Fitness is broadly correlated with the predicted fraction of correctly folded tRNA molecules, revealing a biophysical basis of the fitness landscape.