Horizontal gene transfer potentiates adaptation by reducing selective constraints on the spread of genetic variation.

Horizontal gene transfer (HGT) confers the rapid acquisition of novel traits and is pervasive throughout microbial evolution. Despite the central role of HGT, the evolutionary forces that drive the dynamics of HGT alleles in evolving populations are poorly understood. Here, we show that HGT alters the evolutionary dynamics of genetic variation, so that deleterious genetic variants, including antibiotic resistance genes, can establish in populations without selection. We evolve antibiotic-sensitive populations of the human pathogen in an environment without antibiotic but with HGT from an antibiotic-resistant isolate of We find that HGT increases the rate of adaptation, with most horizontally transferred genetic variants establishing at a low frequency in the population. When challenged with antibiotic, this low-level variation potentiates adaptation, with HGT populations flourishing in conditions where nonpotentiated populations go extinct. By extending previous models of evolution under HGT, we evaluated the conditions for the establishment and spread of HGT-acquired alleles into recipient populations. We then used our model to estimate parameters of HGT and selection from our experimental evolution data. Together, our findings show how HGT can act as an evolutionary force that facilitates the spread of nonselected genetic variation and expands the adaptive potential of microbial populations.