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Essential Bacterial Functions Encoded by Gene Pairs^,||

Helena B. Thomaides,^1* Ella J. Davison,^1, Lisa Burston,^1, Hazel Johnson,¹ David R. Brown,¹ Alison C. Hunt,^2,¶ Jeffery Errington,^2, and Lloyd Czaplewski¹

Prolysis Ltd., Begbroke Science Park, Oxfordshire, United Kingdom,¹ Sir William Dunn School of Pathology, University of Oxford, Oxford, United Kingdom²

Received 30 August 2006/ Accepted 27 October 2006

To address the need for new antibacterials, a number of bacterial genomes have been systematically disrupted to identify essential genes. Such programs have focused on the disruption of single genes and may have missed functions encoded by gene pairs or multiple genes. In this work, we hypothesized that we could predict the identity of pairs of proteins within one organism that have the same function. We identified 135 putative protein pairs in Bacillus subtilis and attempted to disrupt the genes forming these, singly and then in pairs. The single gene disruptions revealed new genes that could not be disrupted individually and other genes required for growth in minimal medium or for sporulation. The pairwise disruptions revealed seven pairs of proteins that are likely to have the same function, as the presence of one protein can compensate for the absence of the other. Six of these pairs are essential for bacterial viability and in four cases show a pattern of species conservation appropriate for potential antibacterial development. This work highlights the importance of combinatorial studies in understanding gene duplication and identifying functional redundancy.

Published ahead of print on 17 November 2006.

^|| Supplemental material for this article may be found at http://jb.asm.org/.

Present address: OCTO, Department of Clinical Pharmacology, Radcliffe Infirmary, Woodstock Road, Oxford OX2 6HE, United Kingdom.

Present address: GPAR, Building 20 GlaxoSmithKline, Greenford Road, Greenford, Middlesex UB6 0HE, United Kingdom.

^¶ Present address: Department of Medical Microbiology, Aberdeen Royal Infirmary, Foresterhill, Aberdeen AB25 2ZN, United Kingdom.

Present address: Institute for Cell and Molecular Biosciences, The Medical School, University of Newcastle, Catherine Cookson Building, Framlington Place, Newcastle NE2 4HH, United Kingdom.

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