Archaea are more hospitable hosts for mobile inteins than bacteria

Intervening proteins, or inteins, are mobile genetic elements characterized by their ability to rearrange peptide bonds through a post-translational, self-splicing reaction. Here, we expand the scope of a prior investigation to reexamine the distribution of inteins across archaea and bacteria. This update represents 20- and 50-fold increases in archaeal and bacterial genomes, respectively. In accordance with previous findings, inteins are enriched in DNA replication, recombination, and repair (RRR) proteins, but they are substantially more prevalent in archaea than bacteria, a difference twice that previously reported. Moreover, mini-inteins lacking homing endonucleases (HENs) are more common in bacterial inteins, suggesting bacterial inteins undergo HEN domain loss more frequently than archaeal inteins. This reduction in the prevalence of HENs, the drivers of intein mobility, offers a potential explanation for the lower density of inteins in bacteria than in archaea. Furthermore, certain classes of bacterial intein-containing proteins primarily contain mini-inteins rather than full-length inteins. The enrichment of mini-inteins within certain bacterial protein classes suggests that HEN domains may impose a greater functional cost in these proteins, creating selective pressure for HEN domain loss and resulting in reduced intein mobilityIMPORTANCEInteins are translated within host proteins and removed via a self-mediated splicing reaction. Prior comparative genomic analysis established that inteins are abundant in both bacteria and archaea, and that their distribution is strongly biased toward proteins involved in DNA transactions. Utilizing genomes made available over the last decade, this work increases the number of putative inteins by over twenty-fold. By investigating the distribution of inteins that can spread throughout/between genomes compared to those that have lost their ability to act as mobile elements, we provide a possible explanation for the higher abundance of inteins in archaea than bacteria. This work not only highlights that archaea are more hospitable intein hosts than bacteria but also serves to update the catalog of known prokaryotic inteins, which will function as a resource to the communities interested in inteins as mobile elements, tools in protein engineering, antimicrobial targets, and post-translational regulatory elements.