Li Chuan, Qian Wenfeng, Maclean Calum J, Zhang Jianzhi
Department of Ecology and Evolutionary Biology, University of Michigan, Ann Arbor, MI 48109, USA.
Science. 2016 May 13;352(6287):837-40. doi: 10.1126/science.aae0568. Epub 2016 Apr 14.
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 quantified Darwinian fitness under a high-temperature challenge for more than 65,000 yeast strains, each carrying a unique variant of the single-copy tRNA(CCU)(Arg) gene at its native genomic location. Approximately 1% of single point mutations in the gene were beneficial and 42% were deleterious. Almost half of all mutation pairs exhibited statistically significant epistasis, which had a strong negative bias, except when the mutations occurred at Watson-Crick paired sites. Fitness was broadly correlated with the predicted fraction of correctly folded transfer RNA (tRNA) molecules, thereby revealing a biophysical basis of the fitness landscape.
适应度景观描述了基因型与适应度的关系，是进化轨迹的主要决定因素。然而，巨大的基因型空间，加上测量适应度的困难，阻碍了对适应度景观的实证确定。我们结合精确的基因替换和下一代测序技术，对65000多个酵母菌株在高温挑战下的达尔文适应度进行了量化，每个菌株在其天然基因组位置携带单拷贝tRNA(CCU)(Arg)基因的独特变体。该基因中约1%的单点突变是有益的，42%是有害的。几乎所有突变对中有一半表现出具有统计学意义的上位性，除了突变发生在沃森-克里克配对位点时，这种上位性具有很强的负偏差。适应度与预测的正确折叠的转运RNA（tRNA）分子比例广泛相关，从而揭示了适应度景观的生物物理基础。
