Background: Reconstructing complete ancestral genomes (at least in terms of their gene inventory and arrangement) is attracting much interest due to the rapidly increasing availability of whole genome sequences. While modest successes have been reported for mammalian and even vertebrate genomes, more divergent groups continue to pose a stiff challenge, mostly because current models of genomic evolution support too many choices.Results: We describe a novel type of genomic signature based on rearrangements that characterizes evolutionary changes that must be common to all minimal rearrangement scenarios; by focusing on global patterns of rearrangements, such signatures bypass individual variations and sharply restrict the search space. We present theresults of extensive simulation studies demonstrating that these signatures can be used to reconstruct accurate ancestral genomes and phylogenies even for widely divergent collections.Conclusion: Focusing on genome triples rather than genomes pairs unleashes the full power of evolutionary analysis. Our genomic signature captures shared evolutionary events and thus can form the basis of a robust analysis and reconstruction of evolutionary history.
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