Resource conservation manifests in the genetic code

Nutrient limitation drives competition for resources across organisms. However, much is unknown about how selective pressures resulting from nutrient limitation shape microbial coding sequences. Here, we study this “resource-driven selection” by using metagenomic and single-cell data of marine microbes, alongside environmental measurements. We show that a significant portion of the selection exerted on microbes is explained by the environment and is associated with nitrogen availability. Notably, this resource conservation optimization is encoded in the structure of the standard genetic code, providing robustness against mutations that increase carbon and nitrogen incorporation into protein sequences. This robustness generalizes to codon choices from multiple taxa across all domains of life, including the human genome.