Selection-Driven Gene Loss in Bacteria

Gene loss by deletion is a common evolutionary process in bacteria, as exemplified by bacteria with small genomes that have evolved from bacteria with larger genomes by reductive processes. The driving force(s) for genome reduction remains unclear, and here we examined the hypothesis that gene loss is selected because carriage of superfluous genes confers a fitness cost to the bacterium. In the bacterium Salmonella enterica, we measured deletion rates at 11 chromosomal positions and the fitness effects of several spontaneous deletions. Deletion rates varied over 200-fold between different regions with the replication terminus region showing the highest rates. Approximately 25% of the examined deletions caused an increase in fitness under one or several growth conditions, and after serial passage of wild-type bacteria in rich medium for 1,000 generations we observed fixation of deletions that substantially increased bacterial fitness when reconstructed in a non-evolved bacterium. These results suggest that selection could be a significant driver of gene loss and reductive genome evolution. The mechanisms and driving forces involved in reductive evolution and loss of non-used gene functions are still largely unknown. Since most deletions are thought to have a negative effect on fitness, it is thought that deletions accumulate by chance, via non-adaptive genetic drift combined with an associated underlying mutational deletion bias. Another possibility is that an adaptive process drives gene loss because superfluous genes confer a fitness cost to the bacterium, providing positive selection for gene loss. Here we have tested the latter idea, and our results show that a surprisingly high fraction of random deletions introduced into the Salmonella chromosome do in fact increase fitness as measured by exponential growth rate. Furthermore, when Salmonella is grown for many generations in a rich growth medium, fitness-increasing deletions accumulate in the population. Our results suggest that selection as well as non-adaptive processes might drive genome reduction and that for certain chromosomal regions gene loss may occur by a rapid adaptive process.