Impact of a homing intein on recombination frequency and organismal fitness

Abstract

Inteins are parasitic genetic elements that excise themselves at the protein level by self-splicing, allowing the formation of functional, nondisrupted proteins. Many inteins contain a homing endonuclease (HEN) domain and rely on its activity for horizontal propagation. However, successful invasion of an entire population will make this activity redundant, and the HEN domain is expected to degenerate quickly under these conditions. Several theories have been proposed for the continued existence of the both active HEN and noninvaded alleles within a population. However, to date, these models were not directly tested experimentally. Using the natural cell fusion ability of the halophilic archaeon Haloferax volcanii we were able to examine this question in vivo, by mating polB intein-positive [insertion site c in the gene encoding DNA polymerase B (polB-c)] and intein-negative cells and examining the dispersal efficiency of this intein in a natural, polyploid population. Through competition between otherwise isogenic intein-positive and intein-negative strains we determined a surprisingly high fitness cost of over 7% for the polB-c intein. Our laboratory culture experiments and samples taken from Israel's Mediterranean coastline show that the polB-c inteins do not efficiently take over an inteinless population through mating, even under ideal conditions. The presence of the HEN/intein promoted recombination when intein-positive and intein-negative cells were mated. Increased recombination due to HEN activity contributes not only to intein dissemination but also to variation at the population level because recombination tracts during repair extend substantially from the homing site. . HENs contribute to the horizontal transmission of these selfish elements into intronless or inteinless alleles, by cleaving the vacant allele to induce homologous recombination or reverse transcription, where the allele containing the intron or intein serves as template. Thus, the intein or intron effectively invades the vacant site and can later be passed on to daughter cells vertically.Paradoxically, if a HEN is highly successful in invading cells, it will saturate all target cells, and then its activity will no longer be under purifying selection. This may result in degeneration of the HEN domain due to accumulation of mutations and will prevent the future horizontal propagation of the intein in question. This phenomenon has been observed in group I introns of bacteriophages (7, 8), eukaryotes (9), and archaea (10). However, active HENs are often observed, and in most natural populations surveyed to date, there are in fact strains with inteins (or introns) containing degenerate HENs, whereas other isolates maintain a fully intact HEN (9). The homing cycle model (11, 12) resolves this paradox by hypothesizing that after the intein-/intron-containing allele has been fixed in the population and after the HEN has completely decayed due to the lack of selection for function of HEN activity, the splicing element (either intron or intein) ...

Selection-based model of prokaryote pangenomes

“…This is likely the case for some MGEs and lysogenic viruses, what we call ‘infectious’ genes, which are most likely deleterious but gained at high rates. For example, deleterious polymorphisms can become prevalent in a bacterial population due to the effect of high recombination mediated by conjugative plasmids 32 , and inteins with high fitness costs seem to be maintained in genomes 33 .…”

Protein splicing of a recombinase intein induced by ssDNA and DNA damage

“…Found in approximately one-quarter of bacterial and one-half of archaeal genomes (Novikova et al 2016), inteins have been considered as purely selfish elements (Naor et al 2016). However, 70% of inteins occur in ATP-binding proteins (Novikova et al 2016), and splicing can be regulated by environmental stresses (Callahan et al 2011;Topilina et al 2015a,b;Reitter et al 2016), suggesting that some inteins have evolved to regulate host protein function.…”

Eimeria tenella Eimeria-specific protein that interacts with apical membrane antigen 1 (EtAMA1) is involved in host cell invasion

“…Inteins, also called protein introns, are parasitic genetic elements that excise themselves at the protein level by self-splicing, allowing the formation of functional, nondisrupted proteins [37]. These data suggest that its functions may be regulated by posttranslational modi cation.…”