Few quantitative measures of genome architecture or organization exist to support assumptions of differences between microorganisms that are broadly defined as being free-living or pathogenic. General principles about complete proteomes exist for codon usage, amino acid biases and essential or core genes. Genome-wide shifts in amino acid usage between free-living and pathogenic microorganisms result in fundamental differences in the complexity of their respective proteomes that are size and gene content independent. These differences are evident across broad phylogenetic groups–a result of environmental factors and population genetic forces rather than phylogenetic distance. A novel comparative analysis of amino acid usage–utilizing linguistic analyses of word frequency in language and text–identified a global pattern of higher peptide word repetition in 376 free-living versus 421 pathogen genomes across broad ranges of genome size, G+C content and phylogenetic ancestry. This imprint )