Methods Mauve Multiple Alignment of Conserved Genomic Sequence With Rearrangements.pdf

Mauve: Multiple Alignment of Conserved Genomic Sequence With Rearrangements Aaron C.E. Darling,1,2,6 Bob Mau,2,3 Frederick R. Blattner,4,5 and Nicole T. Perna2,5 1Department of Computer Science, 2Department of Animal Health and Biomedical Sciences, 3Department of Oncology, 4Department of Genetics, and 5Genome Center of Wisconsin, University of Wisconsin–Madison, Madison, Wisconsin 53706, USA As genomes evolve, they undergo large-scale evolutionary processes that present a challenge to sequence comparison not posed by short sequences. Recombination causes frequent genome rearrangements, horizontal transfer introduces new sequences into bacterial chromosomes, and deletions remove segments of the genome. Consequently, each genome is a mosaic of unique lineage-specific segments, regions shared with a subset of other genomes and segments conserved among all the genomes under consideration. Furthermore, the linear order of these segments may be shuffled among genomes. We present methods for identification and alignment of conserved genomic DNA in the presence of rearrangements and horizontal transfer. Our methods have been implemented in a software package called Mauve. Mauve has been applied to align nine enterobacterial genomes and to determine global rearrangement structure in three mammalian genomes. We have evaluated the quality of Mauve alignments and drawn comparison to other methods through extensive simulations of genome evolution. [Supplemental material is available online at . The source code and binaries are freely available for academic and nonprofit research. Commercial licenses are also available. See /mauve for more details.] The recent determination of numerous bacterial and eukaryotic genome sequences poses new challenges for comparative se- quence analysis. In addition to identifying local changes in the sequences of individual genes, the availability of genome se- quences provides a basis for comparison of the structure and organization of genomes as a