The paper introduces Mauve, a software package for aligning multiple genomes in the presence of rearrangements and horizontal transfers. Mauve identifies conserved genomic regions, rearrangements, and inversions, and performs traditional multiple sequence alignment to identify nucleotide substitutions and small insertions and deletions (indels). The method uses locally collinear blocks (LCBs) as anchors for alignment, allowing for the identification of conserved regions even in the presence of rearrangements. Mauve has been applied to align nine enterobacterial genomes and to determine global rearrangement structure in three mammalian genomes. The authors evaluate the quality of Mauve alignments through extensive simulations of genome evolution, comparing it to other methods such as MultiLAGAN and Shuffle-LAGAN. Mauve is found to be more accurate at lower substitution rates and better suited for aligning closely related sequences with modest amounts of nucleotide substitution or inversion. The paper also discusses the limitations and future improvements of the method, highlighting the importance of considering large-scale evolutionary events in genome comparison.The paper introduces Mauve, a software package for aligning multiple genomes in the presence of rearrangements and horizontal transfers. Mauve identifies conserved genomic regions, rearrangements, and inversions, and performs traditional multiple sequence alignment to identify nucleotide substitutions and small insertions and deletions (indels). The method uses locally collinear blocks (LCBs) as anchors for alignment, allowing for the identification of conserved regions even in the presence of rearrangements. Mauve has been applied to align nine enterobacterial genomes and to determine global rearrangement structure in three mammalian genomes. The authors evaluate the quality of Mauve alignments through extensive simulations of genome evolution, comparing it to other methods such as MultiLAGAN and Shuffle-LAGAN. Mauve is found to be more accurate at lower substitution rates and better suited for aligning closely related sequences with modest amounts of nucleotide substitution or inversion. The paper also discusses the limitations and future improvements of the method, highlighting the importance of considering large-scale evolutionary events in genome comparison.