The dynamics of gene copy-number mutations: transient changes with long-lasting consequences

Abstract Gene copy-number mutations are frequent and prevalent yet often overlooked. While initially considered to be the neutrally evolving raw material needed for the emergence of new genes through the process of gene duplication and divergence, recent technical advances and renewed interest start to unravel a fundamentally different picture for duplications in bacteria: rather than being neutral, duplications have strong direct and indirect fitness effects, and rather than giving rise to evolutionary novelty through protein family expansions, duplications allow to transiently simply make more of the same. Tandem duplications arise at frequencies orders of magnitude higher than single nucleotide polymorphisms (SNPs), and they collapse at an even higher rate still. Understanding the biological idiosyncrasies of copy-number mutations is pivotal to understanding their fundamental role in bacterial evolution. Having multiple copies of a gene influences its evolutionary dynamics in surprising ways, slowing down divergence, acting along with purifying selection as a force of conservation, and facilitating “bet-hedging” in fluctuating environments or under diversifying selection. Paying careful attention to structural variation in genomic sequence analyses will yield a more comprehensive understanding of bacterial evolution, especially when it comes to the emergence of novel bacterial lineages, such as human pathogens.