RT Journal
A1 Kimelman, Aya
A1 Levy, Asaf
A1 Sberro, Hila
A1 Kidron, Shahar
A1 Leavitt, Azita
A1 Amitai, Gil
A1 Yoder-Himes, Deborah R.
A1 Wurtzel, Omri
A1 Zhu, Yiwen
A1 Rubin, Edward M.
A1 Sorek, Rotem
T1 A vast collection of microbial genes that are toxic to bacteria
JF Genome Research 
JO Genome Research 
YR 2012 
FD April 01 
VO 22 
IS 4 
SP 802 
OP 809 
DO 10.1101/gr.133850.111 
UL http://genome.cshlp.org/content/22/4/802.abstract 
AB In the process of clone-based genome sequencing, initial assemblies frequently contain cloning gaps that can be resolved using cloning-independent methods, but the reason for their occurrence is largely unknown. By analyzing 9,328,693 sequencing clones from 393 microbial genomes, we systematically mapped more than 15,000 genes residing in cloning gaps and experimentally showed that their expression products are toxic to the Escherichia coli host. A subset of these toxic sequences was further evaluated through a series of functional assays exploring the mechanisms of their toxicity. Among these genes, our assays revealed novel toxins and restriction enzymes, and new classes of small, non-coding toxic RNAs that reproducibly inhibit E. coli growth. Further analyses also revealed abundant, short, toxic DNA fragments that were predicted to suppress E. coli growth by interacting with the replication initiator DnaA. Our results show that cloning gaps, once considered the result of technical problems, actually serve as a rich source for the discovery of biotechnologically valuable functions, and suggest new modes of antimicrobial interventions.