The type of amino acid substitutions reported in bacterial variants were similar to human variants (Figure ). These featured many disruptive amino acid substitutions (91.53% in bacteria and 89.67% in human), either affecting the size or polarity of the original amino acid or, in most cases, both. To further characterise the disruptive potential of each amino acid substitution, we calculated the Epstein coefficient of difference , which is higher for more disruptive changes. In line with the previous observations, the Epstein coefficient of difference for most of the variants was higher than 0.4 (50.00% of the bacterial and 55.30% of the human variants), thus indicating changes in amino acid properties that would likely affect the protein's function. On the other hand, viral variants featured a larger proportion of conservative amino acid substitutions (17.81%, Figure ). This observation was also backed up by a lower proportion of amino acid substitutions with an Epstein coefficient of difference higher than 0.4 (41.21%), even when the size or polarity was affected. From a biological perspective, organisms with a higher mutation rate, such as viruses, are indeed prone to accumulate fewer damaging substitutions than organisms with a lower mutation rate subjected to more checkpoints, such as humans.