Idiosyncratic purifying selection on metabolic enzymes in the long-term evolution experiment withEscherichia coli

Abstract

Bacteria, Archaea, and Eukarya all share a common set of metabolic reactions. This implies that the function and topology of central metabolism has been evolving under purifying selection over deep time. Central metabolism may similarly evolve under purifying selection during longterm evolution experiments, although it is unclear how long such experiments would have to run (decades, centuries, millennia) before signs of purifying selection on metabolism appear. I hypothesized that central and superessential metabolic enzymes would show evidence of purifying selection in the long-term evolution experiment with Escherichia coli (LTEE), in which 12 initially identical bacterial populations have been evolving in the laboratory for more than 30 years and 60,000 bacterial generations. I also hypothesized that enzymes that specialize on single substrates would show stronger evidence of purifying selection in the LTEE than generalist enzymes that catalyze multiple reactions. I tested these hypotheses by analyzing metagenomic time series covering 60,000 generations of the LTEE. I find mixed support for these hypotheses: patterns of purifying selection on metabolic enzymes, at least after 60,000 generations of experimental evolution, are largely idiosyncratic and population-specific.Significance StatementPurifying selection conserves organismal function over evolutionary time. I looked for evidence of purifying selection on metabolic enzymes in an ongoing long-term evolution experiment with E. coli. While some populations show signs of purifying selection, the overall pattern is inconsistent. To explain this finding, I propose that each population’s metabolism is evolving in a molecular game of Jenga. In this conceptual model, loss-of-function mutations degrade costly, redundant, and inessential metabolic functions, after which purifying selection begins to dominate. The threshold at which purifying selection activates depends on the idiosyncratic trajectory of lost redundancies in each population.

Parallel evolution of mutational fitness effects over 50,000 generations

“…Instead, this parallelism implies that these changes in gene essentiality during the LTEE were favored by natural selection. This selection may have acted directly on gene essentiality or, more likely in our view, the changes in essentiality might have emerged from selection to refine the complex network of interactions present in any cell and thereby adapt that network to the specific LTEE environment ( 50 , 51 ).…”