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Background  Recent comparative genomic studies claim local syntenic gene-interleaving relationships in  Ashbya gossypii  and  Kluyveromyces waltii  are compelling evidence for an ancient whole-genome duplication event in  Saccharomyces cerevisiae . We here test, using Hannenhalli-Pevzner rearrangement algorithms that address the multiple genome rearrangement problem, whether syntenic patterns are proof of paleopolyploidization.    Results  We focus on (1) pairwise comparison of gene arrangement sequences in  A. gossypii  and  S. cerevisiae , (2) reconstruction of gene arrangements ancestral to  A. gossypii ,  S. cerevisiae , and  K. waltii , (3) synteny patterns arising within and between lineages, and (4) expected gene orientation of duplicate gene sets. The existence of syntenic patterns between ancestral gene sets and  A. gossypii ,  S. cerevisiae , and  K. waltii , and other evidence, suggests that gene-interleaving relationships are the natural consequence of topological rearrangements in chromosomes and that a more gradual scenario of genome evolution involving segmental duplication and recombination constitutes a more parsimonious explanation. Furthermore, phylogenetic trees reconstructed under alternative hypotheses placed the putative whole-genome duplication event after the divergence of the  S. cerevisiae  and  K. waltii  lineages, but in the lineage leading to  K. waltii . This is clearly incompatible with an ancient genome duplication event in  S. cerevisiae .    Conclusion  Because the presence of syntenic patterns appears to be a condition that is necessary, but not sufficient, to support the existence of the whole-genome duplication event, our results prompt careful re-evaluation of paleopolyploidization in the yeast lineage and the evolutionary meaning of syntenic patterns.    Reviewers  This article was reviewed by Kenneth H. Wolfe (nominated by Nicolas Galtier), Austin L. Hughes (nominated by Eugene Koonin), Mikhail S. Gelfand, and Mark Gerstein.

Gene-interleaving patterns of synteny in the Saccharomyces cerevisiae genome: are they proof of an ancient genome duplication event?