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Global fitness landscapes of the Shine-Dalgarno sequence.
Genome Research ( IF 6.2 ) Pub Date : 2020-05-01 , DOI: 10.1101/gr.260182.119
Syue-Ting Kuo , Ruey-Lin Jahn , Yuan-Ju Cheng , Yi-Lan Chen , Yun-Ju Lee , Florian Hollfelder , Jin-Der Wen , Hsin-Hung David Chou

Shine-Dalgarno sequences (SD) in prokaryotic mRNA facilitate protein translation by pairing with rRNA in ribosomes. Although conventionally defined as AG-rich motifs, recent genomic surveys reveal great sequence diversity, questioning how SD functions. Here, we determined the molecular fitness (i.e., translation efficiency) of 49 synthetic 9-nt SD genotypes in three distinct mRNA contexts in Escherichia coli We uncovered generic principles governing the SD fitness landscapes: (1) Guanine contents, rather than canonical SD motifs, best predict the fitness of both synthetic and endogenous SD; (2) the genotype-fitness correlation of SD promotes its evolvability by steadily supplying beneficial mutations across fitness landscapes; and (3) the frequency and magnitude of deleterious mutations increase with background fitness, and adjacent nucleotides in SD show stronger epistasis. Epistasis results from disruption of the continuous base pairing between SD and rRNA. This "chain-breaking" epistasis creates sinkholes in SD fitness landscapes and may profoundly impact the evolution and function of prokaryotic translation initiation and other RNA-mediated processes. Collectively, our work yields functional insights into the SD sequence variation in prokaryotic genomes, identifies a simple design principle to guide bioengineering and bioinformatic analysis of SD, and illuminates the fundamentals of fitness landscapes and molecular evolution.

中文翻译:

Shine-Dalgarno序列的全球健身景观。

原核mRNA中的Shine-Dalgarno序列(SD)通过与核糖体中的rRNA配对来促进蛋白质翻译。尽管通常被定义为富含AG的基序,但最近的基因组调查显示出巨大的序列多样性,质疑SD的功能。在这里,我们确定了大肠杆菌中三种不同的mRNA上下文中49种合成的9-nt SD基因型的分子适应性(即翻译效率)。我们发现了控制SD适应性格局的通用原理:(1)鸟嘌呤含量,而不是规范的SD模体,最好地预测合成和内生SD的适应性;(2)SD的基因型-适合度相关性通过在整个健身环境中稳定地提供有益的突变来促进其进化;(3)有害突变的频率和强度随背景适应度的增加而增加,SD中的相邻核苷酸表现出较强的上皮性。上位性源自SD和rRNA之间连续碱基配对的破坏。这种“断链”上位性在SD适应环境中产生了漏洞,并可能深刻影响原核翻译起始和其他RNA介导的过程的进化和功能。总的来说,我们的工作提供了对原核基因组SD序列变异的功能性见解,确定了指导SD的生物工程和生物信息学分析的简单设计原则,并阐明了适应性景观和分子进化的基础。上位性会在SD适应性景观中产生漏洞,并可能深刻影响原核翻译起始和其他RNA介导的过程的进化和功能。总的来说,我们的工作提供了对原核基因组SD序列变异的功能性见解,确定了指导SD的生物工程和生物信息学分析的简单设计原则,并阐明了适应性景观和分子进化的基础。上位性会在SD适应性景观中产生漏洞,并可能深刻影响原核翻译起始和其他RNA介导的过程的进化和功能。总的来说,我们的工作提供了对原核基因组SD序列变异的功能性见解,确定了指导SD的生物工程和生物信息学分析的简单设计原则,并阐明了适应性景观和分子进化的基础。
更新日期:2020-05-01
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