Molecular Biology of Archaea II Homing endonucleases residing within inteins: evolutionary puzzles awaiting genetic solutions

Abstract

Abstract Inteins are selfish genetic elements that disrupt the sequence of protein-coding genes and are excised post-translationally. Most inteins also contain a HEN (homing endonuclease) domain, which is important for their horizontal transmission. The present review focuses on the evolution of inteins and their nested HENs, and highlights several unsolved questions that could benefit from molecular genetic approaches. Such approaches can be well carried out in halophilic archaea, which are naturally intein-rich and have highly developed genetic tools for their study. In particular, the fitness effects of habouring an intein/HEN can be tested in direct competition assays, providing additional insights that will improve current evolutionary models. HENs (homing endonucleases) HENs are a large and diverse class of selfish elements found in archaea, bacteria and lower eukaryotes, and their respective viruses. HENs recognize and cleave specifically long target sequences (12-40 bp) that typically occur only once in a given genome Mutualism between selfish elements Although it is obvious that inteins can profit from horizontal invasion, how and why the HEN benefits from its association with the intein is less obvious. Since HENs typically confer no selective advantage upon their host organism, they can only persist as long as the rate of their dissemination surpasses the rate of their degeneration via genetic drift or counterselection. The rate of dissemination is in turn dependent on the availability of homing targets, which are also subjects of mutation and selection. If cleavage by the HEN is by any degree toxic to the host, mutations in the target site may be selected that prevent it from being recognized or cleaved