A Likely Pathway for Formation of Mobile Group I Introns

Bonocora, Richard P.; Shub, David A.

doi:10.1016/j.cub.2009.01.033

Cited by 45 publications

(52 citation statements)

References 43 publications

(43 reference statements)

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“…Like the bypass sequence, the 5′ ends of many bacteriophage introns begin with an in-frame stop codon, which is part of the base-paired stem (P1) with which all group I introns begin (21,22). Furthermore, like the insertion sites of most group I introns (12,(23)(24)(25), the bypass sequence is inserted into a highly conserved sequence of an essential protein, the Mg 2+ -binding region at the active site of type II topoisomerases (26) (Fig. 1B).…”

Section: Origin Of the Bypassmentioning

confidence: 99%

“…2). The SKX and Pol mobA sequences are identical; the only differences from the T4 sequence are a synonymous G-to-A third position substitution in codon 156 and an A-to-G substitution at the second position of codon 169, changing threonine to alanine.Free-standing homing endonucleases (i.e., those not encoded within a group I intron or intein) cleave the DNA of close relatives lacking the endonuclease gene, usually in a gene adjacent to the site of endonuclease gene insertion (12)(13)(14), and are copied into the recipient genome via recombination-mediated DNA repair, a process that has been called "homing" (for recent reviews, see refs. 14 and 15).…”

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confidence: 99%

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A homing endonuclease and the 50-nt ribosomal bypass sequence of phage T4 constitute a mobile DNA cassette

Bonocora

Zeng

Abel

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

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Since its initial description more than two decades ago, the ribosome bypass (or "hop") sequence of phage T4 stands out as a uniquely extreme example of programmed translational frameshifting. The gene for a DNA topoisomerase subunit of T4 has been split by a 1-kb insertion into two genes that retain topoisomerase function. A second 50-nt insertion, beginning with an inphase stop codon, is inserted near the start of the newly created downstream gene 60. Instead of terminating at this stop codon, approximately half of the ribosomes skip 50 nucleotides and continue translation in a new reading frame. However, no functions, regulatory or otherwise, have been imputed for the truncated peptide that results from termination at codon 46 or for the bypass sequence itself. Moreover, how this unusual mRNA organization arose and why it is maintained have never been explained. We show here that a homing endonuclease (MobA) is encoded in the insertion that created gene 60, and the mobA gene together with the bypass sequence constitute a mobile DNA cassette. The bypass sequence provides protection against self-cleavage by the nuclease, whereas the nuclease promotes horizontal spread of the entire cassette to related bacteriophages. Group I introns frequently provide protection against self-cleavage by associated homing endonucleases. We present a scenario by which the bypass sequence, which is otherwise a unique genetic element, might have been derived from a degenerate group I intron. bacteriophage gene structure | group I intron | horizontal gene transfer | ribosomal frameshifting | mobile genetic element I n most of the phages of the T4 superfamily, the large subunit of DNA topoisomerase is a single polypeptide encoded by gene 39. However, in phage T4 this gene is disrupted by a 1-kb insertion, creating a truncated gene 39 plus a new gene (gene 60) that encodes the remainder of the topoisomerase subunit (1, 2) ( Fig. 1). Furthermore, the C terminus of the truncated gene 39 and the N terminus of the newly created gene 60 each contain additional amino acid residues (43 and 30, respectively) that were not present in the original gene 39 homologs. These two independently translated proteins interact with the small subunit (encoded by gene 52) to create an enzymatically active topoisomerase (4). A second, 50-nt insertion beginning with an inphase stop codon, is inserted into the newly created downstream gene 60 (2). Instead of terminating at this stop codon, approximately half of the ribosomes skip 50 nucleotides and continue translation in a new reading frame (5). Features involved in this remarkable process include: the stop codon, the codon at which translation resumes, a portion of the pre-hop nascent peptide, a stem-loop at the start of the bypassed sequence, a Shine/Dalgarno-like sequence within the bypassed RNA, and the structure of the bypassed mRNA (5-8).The genome sequence of phage T4 (GenBank accession no. NC_000866) indicated that the insertion into gene 39 contains two ORFs: an apparent H-N-H homing endonuclease ps...

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Section: Origin Of the Bypassmentioning

confidence: 99%

mentioning

confidence: 99%

A homing endonuclease and the 50-nt ribosomal bypass sequence of phage T4 constitute a mobile DNA cassette

Bonocora

Zeng

Abel

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

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“…To this end, HEs are always found inserted in peripheral loops that do not play a role in intron splicing or in intein-domains that are not essential for splicing. Evolutionary forces that drive this process recently came to light when David Shub and colleagues showed that the propensity of introns and HEs for targeting highly conserved sequences within conserved genes might have brought them together (9,119) (Fig. 4).…”

Section: Disparate Origins Convergent Parasitic Strategiesmentioning

confidence: 99%

“…Since bacteriophages have a limited repertoire of conserved genes, it is inevitable that an intron/intein and an HE targeting the same conserved sequence come together in the same phage genome. When this happens, the intron/intein and the freestanding HE can move together from one host to another by a process termed collaborative homing (9,119). A rare recombination event can insert the HE into the intron/intein without affecting its splicing, thereby giving rise to a composite parasitic element.…”

Section: Disparate Origins Convergent Parasitic Strategiesmentioning

confidence: 99%

Group I Introns and Inteins: Disparate Origins but Convergent Parasitic Strategies

Raghavan

Minnick

2009

J Bacteriol

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Genomes of most organisms harbor DNA of foreign origin that has no known function. Since these elements may not contribute to a host's fitness but utilize host resources for their perpetuation, it is appropriate to consider them genetic parasites (4). With the advent of sequencing technologies, a wide variety of parasitic elements have been discovered in bacteria from all environments, including obligate intracellular pathogens (100), which were thought to be shielded from horizontal gene transfer (HGT). Detection of a parasitic genetic element in a genome represents only a snapshot of the continuing and dynamic interplay between the host's attempts to purge the element and the element's ability to persist. These adaptable genetic parasites have evolved mechanisms to overcome defenses (75) of the cellular machinery to ultimately invade, colonize, and replicate within the host. Their success is very evident in the human genome, which consists mostly of such apparently superfluous DNA (65). Even compact bacterial genomes packed with functional genes contain mobile genetic elements (100), underscoring their universality in nature.A number of parasitic genetic elements are found in bacterial genomes, including transposons, insertion sequences, prophages, introns, inteins, and intervening sequences. While bacteria, especially pathogenic bacteria, are well studied, their parasitic genetic elements have not received as much attention. In the past few years, while studying the obligate intracellular pathogen Coxiella burnetii, we came to appreciate the intimate relationship between bacterial hosts and parasitic elements (92,93). In addition, interesting new studies have shed light on the evolutionary histories of group I introns, inteins, and homing endonucleases (HEs) (9, 109) and infused excitement into the field. This minireview, which focuses on the biology and evolution of group I introns and inteins found in bacteria, is an attempt to catalyze interest among bacteriologists in these fascinating genetic parasites. GROUP I INTRONSIntrons are noncoding, intragenic regions that are removed from precursor RNA to form the mature RNA by splicing the exons (coding regions that flank introns) together. They are much more common in eukaryotes than in bacteria (50). Introns are classified into four groups based on splicing mechanisms (47): group I, group II/group III, spliceosomal, and tRNA/archaeal introns. Spliceosomal introns are found in eukaryotes and utilize spliceosomes (large protein-RNA complexes) for splicing (70), whereas tRNA introns splice with the help of specialized enzymes (74). Group I and group II introns are able to self-splice-using different mechanisms-without the aid of any proteins and are thus referred to as ribozymes (104). A self-splicing group I intron from Tetrahymena thermophila was one of the first ribozymes to be described, in the early 1980s (61). Ribozymes are considered legacies of a primordial RNA world, where RNA possessed both informationencoding and catalytic properties, before the adven...

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“…HENs can reside within conserved genes because they are nearly always located within self-splicing selfish elements: either group I introns (ref. 3; for review, see ref. 4), which excise themselves at the mRNA level, or inteins, which splice out of the protein product (ref.…”

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confidence: 99%

Impact of a homing intein on recombination frequency and organismal fitness

Naor

Altman-Price

Soucy

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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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) ...

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A Likely Pathway for Formation of Mobile Group I Introns

Cited by 45 publications

References 43 publications

A homing endonuclease and the 50-nt ribosomal bypass sequence of phage T4 constitute a mobile DNA cassette

A homing endonuclease and the 50-nt ribosomal bypass sequence of phage T4 constitute a mobile DNA cassette

Group I Introns and Inteins: Disparate Origins but Convergent Parasitic Strategies

Impact of a homing intein on recombination frequency and organismal fitness

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