Amino acid auxotrophy, the loss of biosynthetic potential for an amino acid, is a highly prevalent feature of microbial life, yet the evolutionary processes driving its distribution in nature remain unclear. Here, we sought to determine whether auxotrophy emerges as an independent response to nutrient availability or as part of a broader transition in genomic lifestyle. By first predicting auxotrophies through genome-scale metabolic models and flux-balance analysis, and subsequently applying phylogenetically informed statistical frameworks, we tested the predictions of the Black Queen Hypothesis, which posits that auxotrophy evolves as a dynamic response to metabolite availability, and disentangled the signal of convergent environmental selection from the background of shared evolutionary history. This approach reveals that phylogeny is the dominant predictor of auxotrophy, vastly outweighing environmental context. Beyond correcting for ancestry, our analysis uncovered a previously obscured signal of consistent, co-occurring genomic changes: auxotrophies do not occur as independent losses, but rather as part of a broader reorganization of the genome. We show that auxotrophies co-occur significantly more often than predicted by chance and that the probability of loss scales with the number of other auxotrophies. These findings reveal auxotrophy as a feature of a conserved, phylogenetically entrenched lifestyle rather than a transient response to nutrient availability -- inconsistent with the Black Queen Hypothesis and instead aligning with genome streamlining as the overarching driver of metabolic dependency in natural microbial systems.
Henderson, A. et al. · CC-BY 4.0