Horizontally transferred gene clusters in E. coli match size expectations from uber-operons

Adaptation of bacteria occurs predominantly via horizontal gene transfer. While it is widely recognized that horizontal gene acquisitions frequently encompass multiple genes, it is currently unclear what the size distribution of successfully transferred DNA segments looks like and what evolutionary forces shape this distribution. Here, we identified 7,538 gene pairs that were consistently co-gained on the same branches across a phylogeny of 53 E. coli strains. These pairs are significantly enriched in genes that share the same GO annotation. We estimated the genomic distances of these co-gained pairs at the time they were transferred to their host genomes, which shows a sharp upper bound at 30kb. This upper bound is significantly lower than the size limit on gene co-transfers imposed by the carrying capacity of the transfer agents. The observed distance distribution also appears inconsistent with a model based on the co-transfer of genes within operons; instead, we found that the distance distribution of co-transferred genes closely matches the distribution expected from the transfer of uber-operons, i.e., genomic clusters of co-functioning genes beyond operons.