Mycobacteriophages as Incubators for Intein Dissemination and Evolution

ABSTRACT Inteins are self-splicing protein elements that are mobile at the DNA level and are sporadically distributed across microbial genomes. Inteins appear to be horizontally transferred, and it has been speculated that phages may play a role in intein distribution. Our attention turns to mycobac...

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Autores principales:	Danielle S. Kelley, Christopher W. Lennon, Marlene Belfort, Olga Novikova
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2016
Materias:	Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/216301a419c34f67953474ae64a666fd
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spelling	oai:doaj.org-article:216301a419c34f67953474ae64a666fd2021-11-15T15:50:14ZMycobacteriophages as Incubators for Intein Dissemination and Evolution10.1128/mBio.01537-162150-7511https://doaj.org/article/216301a419c34f67953474ae64a666fd2016-11-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.01537-16https://doaj.org/toc/2150-7511ABSTRACT Inteins are self-splicing protein elements that are mobile at the DNA level and are sporadically distributed across microbial genomes. Inteins appear to be horizontally transferred, and it has been speculated that phages may play a role in intein distribution. Our attention turns to mycobacteriophages, which infect mycobacteria, where both phage and host harbor inteins. Using bioinformatics, mycobacteriophage genomes were mined for inteins. This study reveals that these mobile elements are present across multiple mycobacteriophage clusters and are pervasive in certain genes, like the large terminase subunit TerL and a RecB-like nuclease, with the majority of intein-containing genes being phage specific. Strikingly, despite this phage specificity, inteins localize to functional motifs shared with bacteria, such that intein-containing genes have similar roles, like hydrolase activity and nucleic acid binding, indicating a global commonality among intein-hosting proteins. Additionally, there are multiple insertion points within active centers, implying independent invasion events, with regulatory implications. Several phage inteins were shown to be splicing competent and to encode functional homing endonucleases, important for mobility. Further, bioinformatic analysis supports the potential for phages as facilitators of intein movement among mycobacteria and related genera. Analysis of catalytic intein residues finds the highly conserved penultimate histidine inconsistently maintained among mycobacteriophages. Biochemical characterization of a noncanonical phage intein shows that this residue influences precursor accumulation, suggesting that splicing has been tuned in phages to modulate generation of important proteins. Together, this work expands our understanding of phage-based intein dissemination and evolution and implies that phages provide a context for evolution of splicing-based regulation. IMPORTANCE Inteins are mobile protein splicing elements found in critical genes across all domains of life. Mycobacterial inteins are of particular interest because of their occurrence in pathogenic species, such as Mycobacterium tuberculosis and Mycobacterium leprae, which harbor inteins in important proteins. We have discovered a similarity in activities of intein-containing proteins among mycobacteriophages and their intein-rich actinobacterial hosts, with implications for both posttranslational regulation by inteins and phages participating in horizontal intein transfer. Our demonstration of multiple insertion points within active centers of phage proteins implies independent invasion events, indicating the importance of intein maintenance at specific functional sites. The variable conservation of a catalytic splicing residue, leading to profoundly altered splicing rates, points to the regulatory potential of inteins and to mycobacteriophages playing a role in intein evolution. Collectively, these results suggest inteins as posttranslational regulators and mycobacteriophages as both vehicles for intein distribution and incubators for intein evolution.Danielle S. KelleyChristopher W. LennonMarlene BelfortOlga NovikovaAmerican Society for MicrobiologyarticleMicrobiologyQR1-502ENmBio, Vol 7, Iss 5 (2016)
institution	DOAJ
collection	DOAJ
language	EN
topic	Microbiology QR1-502
spellingShingle	Microbiology QR1-502 Danielle S. Kelley Christopher W. Lennon Marlene Belfort Olga Novikova Mycobacteriophages as Incubators for Intein Dissemination and Evolution
description	ABSTRACT Inteins are self-splicing protein elements that are mobile at the DNA level and are sporadically distributed across microbial genomes. Inteins appear to be horizontally transferred, and it has been speculated that phages may play a role in intein distribution. Our attention turns to mycobacteriophages, which infect mycobacteria, where both phage and host harbor inteins. Using bioinformatics, mycobacteriophage genomes were mined for inteins. This study reveals that these mobile elements are present across multiple mycobacteriophage clusters and are pervasive in certain genes, like the large terminase subunit TerL and a RecB-like nuclease, with the majority of intein-containing genes being phage specific. Strikingly, despite this phage specificity, inteins localize to functional motifs shared with bacteria, such that intein-containing genes have similar roles, like hydrolase activity and nucleic acid binding, indicating a global commonality among intein-hosting proteins. Additionally, there are multiple insertion points within active centers, implying independent invasion events, with regulatory implications. Several phage inteins were shown to be splicing competent and to encode functional homing endonucleases, important for mobility. Further, bioinformatic analysis supports the potential for phages as facilitators of intein movement among mycobacteria and related genera. Analysis of catalytic intein residues finds the highly conserved penultimate histidine inconsistently maintained among mycobacteriophages. Biochemical characterization of a noncanonical phage intein shows that this residue influences precursor accumulation, suggesting that splicing has been tuned in phages to modulate generation of important proteins. Together, this work expands our understanding of phage-based intein dissemination and evolution and implies that phages provide a context for evolution of splicing-based regulation. IMPORTANCE Inteins are mobile protein splicing elements found in critical genes across all domains of life. Mycobacterial inteins are of particular interest because of their occurrence in pathogenic species, such as Mycobacterium tuberculosis and Mycobacterium leprae, which harbor inteins in important proteins. We have discovered a similarity in activities of intein-containing proteins among mycobacteriophages and their intein-rich actinobacterial hosts, with implications for both posttranslational regulation by inteins and phages participating in horizontal intein transfer. Our demonstration of multiple insertion points within active centers of phage proteins implies independent invasion events, indicating the importance of intein maintenance at specific functional sites. The variable conservation of a catalytic splicing residue, leading to profoundly altered splicing rates, points to the regulatory potential of inteins and to mycobacteriophages playing a role in intein evolution. Collectively, these results suggest inteins as posttranslational regulators and mycobacteriophages as both vehicles for intein distribution and incubators for intein evolution.
format	article
author	Danielle S. Kelley Christopher W. Lennon Marlene Belfort Olga Novikova
author_facet	Danielle S. Kelley Christopher W. Lennon Marlene Belfort Olga Novikova
author_sort	Danielle S. Kelley
title	Mycobacteriophages as Incubators for Intein Dissemination and Evolution
title_short	Mycobacteriophages as Incubators for Intein Dissemination and Evolution
title_full	Mycobacteriophages as Incubators for Intein Dissemination and Evolution
title_fullStr	Mycobacteriophages as Incubators for Intein Dissemination and Evolution
title_full_unstemmed	Mycobacteriophages as Incubators for Intein Dissemination and Evolution
title_sort	mycobacteriophages as incubators for intein dissemination and evolution
publisher	American Society for Microbiology
publishDate	2016
url	https://doaj.org/article/216301a419c34f67953474ae64a666fd
work_keys_str_mv	AT danielleskelley mycobacteriophagesasincubatorsforinteindisseminationandevolution AT christopherwlennon mycobacteriophagesasincubatorsforinteindisseminationandevolution AT marlenebelfort mycobacteriophagesasincubatorsforinteindisseminationandevolution AT olganovikova mycobacteriophagesasincubatorsforinteindisseminationandevolution
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Mycobacteriophages as Incubators for Intein Dissemination and Evolution

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