“…Gene loss has also been recognized as an important force in genome variation, especially in host-associated microbial populations (37)(38)(39)(40). In particular, several derived pathogens, Salmonella enterica Typhi (32,36) and Shigella (28), and intracellular symbionts, Buchnera (41,42), have been suggested to undergo significant genome reductions. Gene loss has also been identified in free-living microorganisms (43), and it is often assumed that loss is mechanistically simpler than gain when modeling genome evolution (9,33,44,45), although the relative importance of gene gain and loss to variation in the pan-genome is still the subject of debate.…”