Measuring the tolerance of the genetic code to altered codon size
Name
elife-76941-v2.pdf
Description
Published version
Size
4.91 MB
Format
Adobe PDF
Checksum (MD5)
ffff8ec956c63e8e3946a392a20f7091
Author(s)
DeBenedictis, Erika Alden
Söll, Dieter
Esvelt, Kevin M
Date Issued
2022
Journal
eLife
Publisher
eLife Sciences Publications, Ltd
Citation
DeBenedictis, Erika Alden, Söll, Dieter and Esvelt, Kevin M. 2022. "Measuring the tolerance of the genetic code to altered codon size." eLife, 11.
Version
Final published version
Abstract
Translation using four-base codons occurs in both natural and synthetic systems. What constraints contributed to the universal adoption of a triplet codon, rather than quadruplet codon, genetic code? Here, we investigate the tolerance of the Escherichia coli genetic code to tRNA mutations that increase codon size. We found that tRNAs from all 20 canonical isoacceptor classes can be converted to functional quadruplet tRNAs (qtRNAs). Many of these selectively incorporate a single amino acid in response to a specified four-base codon, as confirmed with mass spectrometry. However, efficient quadruplet codon translation often requires multiple tRNA mutations. Moreover, while tRNAs were largely amenable to quadruplet conversion, only nine of the twenty aminoacyl tRNA synthetases tolerate quadruplet anticodons. These may constitute a functional and mutually orthogonal set, but one that sharply limits the chemical alphabet available to a nascent all-quadruplet code. Our results suggest that the triplet codon code was selected because it is simpler and sufficient, not because a quadruplet codon code is unachievable. These data provide a blueprint for synthetic biologists to deliberately engineer an all-quadruplet expanded genetic code.
MIT Department
Program in Media Arts and Sciences (Massachusetts Institute of Technology)
Terms of Use
Creative Commons Attribution 4.0 International license
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.7554/ELIFE.76941
