DNA double-strand breaks (DSBs) are a threat to genome stability. In all domains of life, DSBs are faithfully fixed via homologous recombination. However, recombination requires the presence of an uncut copy of duplex DNA that can be used as a template for repair. Alternate to this, in the absence of a template, eukaryotes and some prokaryotes also utilize Non-homologous end joining (NHEJ) repair.This pathway, or variations of it, can be error-prone. However, it avoids the lethality of a DSB, making NHEJ an important form of repair. Although ubiquitously found in eukaryotes, NHEJ is not universally present in bacteria. It is unclear as to why many prokaryotic systems lack this pathway. To understand what could have led to the current distribution of NHEJ in bacteria, we carried out comparative genomics and phylogenetic analysis across ~6000 sequenced genomes. Our results show that this repair trait is sporadically distributed across the phylogeny, with a few clades that are completely devoid of it.Ancestral reconstruction suggests that NHEJ was absent in the eubacterial ancestor, followed by primary independent gains as well as secondary losses and gains, in different clades across the bacterial history. Further, our analysis suggests that this pattern of occurrence is consistent with the correlated evolution of NHEJ with key genome characteristics of genome size and growth rates; NHEJ presence in bacteria is associated with large genome sizes and / or slow growth rates, with the former being the dominant correlate. Given the central role these traits may play in determining the ability to carry out recombination, it is possible that the evolutionary history of bacterial NHEJ may have been shaped by the requirement for efficient DSB repair.
