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Nucleic Acids Research Advance Access originally published online on March 5, 2009
Nucleic Acids Research 2009 37(8):2560-2573; doi:10.1093/nar/gkp095
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Nucleic Acids Research, 2009, Vol. 37, No. 8 2560-2573
© 2009 The Author(s)
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Genomics

Fractured genes: a novel genomic arrangement involving new split inteins and a new homing endonuclease family

Bareket Dassa1, Nir London2, Barry L. Stoddard3, Ora Schueler-Furman2 and Shmuel Pietrokovski1,*

1Department of Molecular Genetics, the Weizmann Institute of Science, Rehovot 76100, 2Department of Molecular Genetics and Biotechnology, Hebrew University, Hadassah Medical School, Jerusalem 91120, Israel and 3Division of Basic Sciences, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave N. A3-025, Seattle, WA 98109, USA

*To whom correspondence should be addressed. Tel: +972 8 9342747; Fax: +972 8 9344108; Email: shmuel.pietrokovski{at}weizmann.ac.il

Received January 12, 2009. Revised February 4, 2009. Accepted February 4, 2009.

Inteins are genetic elements, inserted in-frame into protein-coding genes, whose products catalyze their removal from the protein precursor via a protein-splicing reaction. Intein domains can be split into two fragments and still ligate their flanks by a trans-protein-splicing reaction. A bioinformatic analysis of environmental metagenomic data revealed 26 different loci with a novel genomic arrangement. In each locus, a conserved enzyme coding region is broken in two by a split intein, with a free-standing endonuclease gene inserted in between. Eight types of DNA synthesis and repair enzymes have this ‘fractured’ organization. The new types of naturally split-inteins were analyzed in comparison to known split-inteins. Some loci include apparent gene control elements brought in with the endonuclease gene. A newly predicted homing endonuclease family, related to very-short patch repair (Vsr) endonucleases, was found in half of the loci. These putative homing endonucleases also appear in group-I introns, and as stand-alone inserts in the absence of surrounding intervening sequences. The new fractured genes organization appears to be present mainly in phage, shows how endonucleases can integrate into inteins, and may represent a missing link in the evolution of gene breaking in general, and in the creation of split-inteins in particular.


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