Global fitness landscapes of the Shine-Dalgarno sequence
Journal
Genome Research
Journal Volume
30
Journal Issue
5
Pages
711-723
Date Issued
2020
Author(s)
Kuo, Syue-Ting
Jahn, Ruey-Lin
Cheng, Yuan-Ju
Chen, Yi-Lan
Lee, Yun-Ju
Hollfelder, Florian
Wen, Jin-Der
Abstract
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.
Type
journal article