Proof and evolutionary analysis of ancient genome duplication in the yeast Saccharomyces cerevisiae


Whole-genome duplication followed by massive gene loss and specialization has long been postulated as a powerful mechanism of evolutionary innovation. Recently, it has become possible to test this notion by searching complete genome sequence for signs of ancient duplication. Here, we show that the yeast Saccharomyces cerevisiae arose from ancient whole-genome duplication, by sequencing and analysing Kluyveromyces waltii, a related yeast species that diverged before the duplication. The two genomes are related by a 1:2 mapping, with each region of K. waltii corresponding to two regions of S. cerevisiae, as expected for whole-genome duplication. This resolves the long-standing controversy on the ancestry of the yeast genome, and makes it possible to study the fate of duplicated genes directly. Strikingly, 95% of cases of accelerated evolution involve only one member of a gene pair, providing strong support for a specific model of evolution, and allowing us to distinguish ancestral and derived functions.

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Figure 1: Model of WGD followed by massive gene loss predicts gene interleaving in sister regions.
Figure 2: Gene and region correspondence with K. waltii reveals WGD.
Figure 3: Duplicated blocks in S. cerevisiae.
Figure 4: Divergence of duplicated gene pairs.


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We thank I. Roberts for providing strains; M. Endrizzi, L.-J. Ma, D. Qi and the staff of the MIT/Whitehead Institute Center for Genome Research who generated the shotgun sequence from Kluyveromyces waltii; J. Butler and the Arachne assembly team who generated the genome assembly; D. Bartel, S. Calvo, J. Galagan, D. Jaffe and J. Vinson for discussions and comments on the manuscript; and G. Fink and A. Murray for discussions and advice.

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Correspondence to Manolis Kellis or Eric S. Lander.

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The authors declare that they have no competing financial interests.

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Supplementary Information

Links to directory containing: S1. Assembly; S2. ORFs; S3. Annotation; S4. Blocks; S5. Poster; S6. Visualization; S7. Dupblocks; S8. Dupgenes; S9. Trees; S10. Centromeres. (HTM 37 kb)

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Kellis, M., Birren, B. & Lander, E. Proof and evolutionary analysis of ancient genome duplication in the yeast Saccharomyces cerevisiae. Nature 428, 617–624 (2004).

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