Beyond ParB: Evolution of the chromosome partitioning protein ParB and discovery of novel CTP-dependent proteins

The precise coordination of cellular processes such as cell-cycle regulation is critical for every organism. Therefore, a vast repertoire of regulatory proteins including proteins regulated by small molecules such as nucleotides has evolved. Recent studies on ParB, a protein involved in bacterial DNA segregation, led to the discovery of a novel class of CTP-dependent molecular switches. Importantly, database searches suggested that the ParB/Srx domain of ParB, which mediates its ability to bind and hydrolyze CTP, may be widely conserved among bacteria and archaea. In this study, we combined bioinformatic and biochemical approaches to identify novel CTP-regulated proteins. Apart from that, we used ancestral sequence reconstruction and biochemical studies to unravel the evolution of ParB-type DNA segregation proteins. We show that ParB is an ancient protein whose core functions were preserved over billions of years of evolution. Collectively, this work highlights the prevalence and importance of ParB/Srx-type CTPases in bacteria, thereby shedding light on a widespread new mode of regulation in bacteria.