Homing endonucleases residing within inteins: evolutionary puzzles awaiting genetic solutions

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 harbouring an intein/HEN can be tested in direct competition assays, providing additional insights that will improve current evolutionary models.

Bacterial Genome Instability

“…Inteins are widespread in bacteria (124)(125)(126)(127)(128)(129)(130)(131)(132)(133)(134)(135)(136). They are peptides of 134 to 608 amino acids encoded in frame within host proteins.…”

“…Homing endonucleases are considered to be the real mobile elements encoded within introns and inteins, but they can also be freestanding in intergenic regions (129,133,136,(158)(159)(160)(161)(162)(163)(164)(165)(166). A homing endonuclease would bring mobility to a splicing element in exchange for the capacity to target conserved genes without being detrimental to the host bacterium.…”

A survey of transposable element classification systems – A call for a fundamental update to meet the challenge of their diversity and complexity

“…Although their discovery dated from the early 80's (Kruger et al, 1982;Garriga and Lambowitz, 1983;Waring and Davies, 1984;Kane et al, 1990;Hirata et al, 1990) self-splicing elements (SSEs), which are DNA segments inserted into expressed host regions, have been virtually ignored by the eukaryotic TE community, despite the fact that SSEs are consistently treated as true TEs in a large body of scientific literature associated with prokaryotes and certain eukaryotic nuclear genomes (Belfort, 2003;Stoddard, 2005;Dassa et al, 2009;Pietrokovski, 2001;Gogarten and Hilario, 2006;Barzel et al, 2011). To date, this has had two major consequences.…”

“…Intein DNA sequences are in-frame insertions into protein coding genes, typically genes that are important for the host genome's survival (Gogarten and Hilario, 2006;Barzel et al, 2011). These sequences insert into highly conserved gene motifs and code for a protein that is able to catalyze both the excision of the intein amino acid sequence post-translation and the ligation of the host protein (the extein, Fig.…”

Sequential formation of two branched intermediates during protein splicing of class three inteins

“…The majority of inteins are bifunctional enzymes that have a homing endonuclease domain as well as a protein splicing domain. The homing endonuclease is responsible for lateral transmission of intein genes, making them parasitic mobile genetic elements (Barzel et al 2011; Novikova et al 2014). Mini-inteins do not have an endonuclease domain, but retain the core protein splicing domain.…”