The easily angered sage Durvasa from Indian mythology represents mistranslating cells. The quiet sages on the left depict normal wild type cells, while the angry ones on the right are the short-fused ‘Durvasas’. Like their namesake who is rather indiscriminate in his cursing and can therefore get into trouble, mistranslating cells incur a cost and are under-represented in the population. However, like the short fused Durvasa, they are prepared to fend off attacks from demons by accumulating stress response molecules (shown as fireballs in the chest). In contrast, the quiet sages are not prepared and are likelier to be killed. The demon represents DNA damage here and the aftermath shows that mistranslating cells show higher survival than their wild type counterparts.

Proteins are critical for cellular function. Mistranslation constitutes a non-genetic change that is ubiquitous and constantly generates protein sequence variability at a high rate (~ 1 in 10,000 incorrect amino acids). The rate at which this occurs is influenced both by genotype and by environment. Although individual proteins altered in this manner (without any change in DNA) cannot be inherited, protein heterogeneity impacts the ability of the cell to grow and divide in a given environment as well as its ability to adapt to new environments in the short and long-term, across both prokaryotic and eukaryotic systems. We showed earlier that mistranslation increases resistance to DNA damage and high temperature (Samhita et al, 2020), increases phenotypic variability (Samhita et al, 2021) and also alters the nature of mutations that arise during exposure to antibiotics (unpublished). We are following up on these observations and attempting to understand the occurrence, distribution and adaptive role of mistranslation in bacterial cells.

Picture featured on the cover page of PLoS Genetics, March 2020.

Picture credit: Pranjal Gupta