The Life-Cycle of Operons

Abstract

Operons are a major feature of all prokaryotic genomes, but how and why operon structures vary is not well understood. To elucidate the life-cycle of operons, we compared gene order between Escherichia coli K12 and its relatives and identified the recently formed and destroyed operons in E. coli. This allowed us to determine how operons form, how they become closely spaced, and how they die. Our findings suggest that operon evolution may be driven by selection on gene expression patterns. First, both operon creation and operon destruction lead to large changes in gene expression patterns. For example, the removal of lysA and ruvA from ancestral operons that contained essential genes allowed their expression to respond to lysine levels and DNA damage, respectively. Second, some operons have undergone accelerated evolution, with multiple new genes being added during a brief period. Third, although genes within operons are usually closely spaced because of a neutral bias toward deletion and because of selection against large overlaps, genes in highly expressed operons tend to be widely spaced because of regulatory fine-tuning by intervening sequences. Although operon evolution may be adaptive, it need not be optimal: new operons often comprise functionally unrelated genes that were already in proximity before the operon formed. In bacteria, adjacent genes are often transcribed together in operons. Which genes are placed together in operons varies greatly across bacteria. This diversity of operon structure can be used to predict the function of genes: genes that are sometimes in an operon are likely to have related functions, even if they are transcribed separately in the organism of interest. However, it has not been clear why this diversity exists or what its consequences are. This work reconstructs evolutionarily recent changes to operon structures in the well-studied bacterium Escherichia coli. Changes in operon structure are shown to be associated with changes in gene expression patterns, so the diversity in operon structure may reflect adaptation to differing lifestyles. Indeed, some of these changes appear to be beneficial to the organism. This work also reconstructs the molecular mechanisms of operon evolution. Understanding these mechanisms should aid other analyses of bacterial genomes. For example, new operons often arise by deleting the DNA between functionally unrelated genes that happen to be near each other. Thus, recently evolved operons should not be used to infer their genes' function. Overall, this work provides a framework for understanding the evolutionary life-cycle of operons.