Exploring the costs of horizontal gene transfer

•Successful horizontal gene transfer (HGT) can lead to phenotypic side effects and inefficiencies.•Costs of HGT arise from multiple genetic and genomic sources.•Magnitude of costs depend on sequence, expression, and strain or environmental context.•Costs of HGT can shift evolutionary dynamics and adaptive landscapes.

Horizontal gene transfer (HGT) is one of the most important evolutionary forces within microbial populations. Although evidence for beneficial fitness effects of HGT is overwhelming, recently acquired regions often function inefficiently within new genomic backgrounds so that each transfer event has the potential to disrupt existing regulatory and physiological networks. Identifying and exploring costs is essential for guiding general discussions about the interplay between selection and HGT, as well as generating hypotheses to explain how HGT affects evolutionary potential through, for example, changing adaptive trajectories. Focusing on costs of HGT as foundations for future studies will enhance exploration at the interface between acquired regions and recipient genomes, including the process of amelioration, and enable experimental evaluation of the role of HGT in structuring genetic diversity across populations.