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A Whole-Genome Shotgun Optical Map of Yersinia pestis Strain KIM

Shiguo Zhou,¹ Wen Deng,² Thomas S. Anantharaman,^1,3 Alex Lim,^1,4 Eileen T. Dimalanta,^1,4 Jun Wang,^1,4 Tian Wu,^1,4 Tao Chunhong,¹ Robert Creighton,¹ Andrew Kile,¹ Erika Kvikstad,¹ Michael Bechner,¹ Galex Yen,¹ Ana Garic-Stankovic,¹ Jessica Severin,¹ Dan Forrest,¹ Rod Runnheim,¹ Chris Churas,¹ Casey Lamers,¹ Nicole T. Perna,^2, Valerie Burland,² Frederick R. Blattner,² Bhubaneswar Mishra,⁵ and David C. Schwartz^1,2,4*

Laboratory for Molecular and Computational Genomics,¹ Department of Chemistry,⁴ Laboratory of Genetics, University of Wisconsin—Madison, Madison, Wisconsin 53706,² Department of Biostatistics and Medical Informatics,³ Courant Institute of Mathematical Sciences, Department of Computer Science, New York University, New York, New York 10012⁵

Received 12 June 2002/ Accepted 12 September 2002

Yersinia pestis is the causative agent of the bubonic, septicemic, and pneumonic plagues (also known as black death) and has been responsible for recurrent devastating pandemics throughout history. To further understand this virulent bacterium and to accelerate an ongoing sequencing project, two whole-genome restriction maps (XhoI and PvuII) of Y. pestis strain KIM were constructed using shotgun optical mapping. This approach constructs ordered restriction maps from randomly sheared individual DNA molecules directly extracted from cells. The two maps served different purposes; the XhoI map facilitated sequence assembly by providing a scaffold for high-resolution alignment, while the PvuII map verified genome sequence assembly. Our results show that such maps facilitated the closure of sequence gaps and, most importantly, provided a purely independent means for sequence validation. Given the recent advancements to the optical mapping system, increased resolution and throughput are enabling such maps to guide sequence assembly at a very early stage of a microbial sequencing project.

Present address: Animal Health and Biomedical Sciences, University of Wisconsin—Madison, Madison, WI 53706.

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