Environmental conditions shape the nature of a minimal bacterial genome

Of the 473 genes in the genome of the bacterium with the smallest genome generated to date, 149 genes have unknown function, emphasising a universal problem; less than 1% of proteins have experimentally determined annotations. Here, we combine the results from state-of-the-art in silico methods for functional annotation and assign functions to 66 of the 149 proteins. Proteins that are still not annotated lack orthologues, lack protein domains, and/ or are membrane proteins. Twenty-four likely transporter proteins are identified indicating the importance of nutrient uptake into and waste disposal out of the minimal bacterial cell in a nutrient-rich environment after removal of metabolic enzymes. Hence, the environment shapes the nature of a minimal genome. Our findings also show that the combination of multiple different state-of-the-art in silico methods for annotating proteins is able to predict functions, even for difficult to characterise proteins and identify crucial gaps for further development. Minimal bacterial genomes still contain hundreds of genes of unknown function. Here the authors use in silico annotation methods and identify the environmental factors shaping a minimal genome.