Environmental perturbations lift the degeneracy of the genetic code
The genetic code is degenerate in that most amino acids are encoded by multiple codons. We found that an environmental perturbation, starvation, lifts the degeneracy of the genetic code. This work was published in PNAS.
Summary: We are using both population and single-cell studies in E. coli to understand the dynamic and state-dependent aspects of degeneracy in the genetic code. At the population level, we found that limitation of the cognate amino acid splits codon families into a hierarchy of associated protein synthesis rates. Some codons maintain their associated protein synthesis rate during this starvation, thus, they are robust to perturbation (e.g CUG, black, in above figure.) Other codons show a substantial decrease in associated protein synthesis rate; they are sensitive to perturbation (e.g. CUA, red, in above figure.) This hierarchy of robust and sensitive codons, established in a synthetic reporter library, explained the measured robustness and sensitivities of synthesis for endogenous proteins. The fitness cost of synonymous mutations in amino acid biosynthesis genes and transcriptional control of sigma factor genes also reflected degeneracy lifting. This work suggests that organisms may use degeneracy lifting as a general strategy to adapt protein synthesis in a fluctuating environment.
Former postdoc Arvind Subramaniam led the population-level study, which was a collaboration with Tao Pan's lab at the University of Chicago and published in PNAS. Current postdoc Lisa Marshall is working on the single-cell aspect of the study.