The main forces driving genome evolution in prokaryotes include gene genesis, lateral gene transfer, and gene loss. Our analysis of protein evolution using SYNERGY does not examine whether orthogroups appearing have arisen by lateral gene transfer or by gene genesis involving duplication and divergence from other orthogroups. A detailed comparison to categorize these orthogroup appearances according to lateral or vertical gene transfer is beyond the scope of this study, but other studies indicate that lateral gene transfer has played a significant role in Mycobacterial evolution and the evolution of pathogenesis [79] [80] [81] [82] [83] .