Factors such as effective population size (Ne) and proteome size modulate the interaction of selection, drift, mutation and recombination for guiding the genome evolution. Prokaryotic genomes are useful for studying these interactions in front of phenomena such as endosymbiosis. The reduced Ne of endosymbionts causes a more effective drift than selection and a more accelerated Muller’s ratchet. As prokaryotes have a deletional bias, the continuous ratchet causes a genome size reduction. Moreover, less effective proteomic selection leads to tRNA redundancy decay producing higher translational selection. This study aims to explain differences of proteomic selection among prokaryotes and their relationship with translational selection. Differences of proteomic selection were estimated by comparing their GCnonsyn constraint. This study shows that GCnonsyn should be measured in front of variations of GCsyn, and GCsyn cannot be used interchangeably with intergenic GCcontent because they have differences due to acquisition of R-M systems. Non-endosymbionts show a stronger proteomic selection than endosymbionts due to Muller’s ratchet and reduced Ne. Intracellular bacteria have stronger proteomic selection than metazoan mitochondria due to small differences of recombination and/or differences of proteomic constraint. In contrast, chloroplasts have similar proteomic selection than non-endosymbionts due to homologous recombination; and their genome size reduction is likely due to migrations of sequences to the nucleus. The estimates of proteomic selection and translational selection demonstrated that both factors are related, being metazoan mitochondria the most conclusive evidence of such relationship. This study demonstrates that GCnosyn vs. GCsyn is an accurate method to estimate differences of proteomic selection among prokaryotes and that patterns of genome evolution among endosymbionts can be very different due to the complicated nature of endosymbiosis.