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Birth of a metabolic gene cluster in yeast by adaptive gene relocation


Although most eukaryotic genomes lack operons, they contain some physical clusters of genes that are related in function despite being unrelated in sequence1,2,3,4,5. How these clusters are formed during evolution is unknown. The DAL cluster is the largest metabolic gene cluster in yeast and consists of six adjacent genes encoding proteins that enable Saccharomyces cerevisiae to use allantoin as a nitrogen source6. We show here that the DAL cluster was assembled, quite recently in evolutionary terms, through a set of genomic rearrangements that happened almost simultaneously. Six of the eight genes involved in allantoin degradation, which were previously scattered around the genome, became relocated to a single subtelomeric site in an ancestor of S. cerevisiae and Saccharomyces castellii. These genomic rearrangements coincided with a biochemical reorganization of the purine degradation pathway, which switched to importing allantoin instead of urate. This change eliminated urate oxidase, one of several oxygen-consuming enzymes that were lost by yeasts that can grow vigorously in anaerobic conditions. The DAL cluster is located in a domain of modified chromatin involving both H2A.Z histone exchange and Hst1-Sum1–mediated histone deacetylation, and it may be a coadapted gene complex formed by epistatic selection.

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Figure 1: The allantoin degradation pathway.
Figure 2: Conservation and disruption of the DAL gene cluster.
Figure 3: Locations of the DAL genes in K. waltii as compared with S. cerevisiae.


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We thank D. Scannell, K. Byrne, J. Gordon, G. Conant, N. Khaldi, B. Cusack, L. Rusche, J. Conery and anonymous referees for comments. This study was supported by Science Foundation Ireland.

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Correspondence to Kenneth H Wolfe.

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Supplementary information

Supplementary Fig. 1

Organization of the DAL clusters of S. cerevisiae aned S. castellii. (PDF 84 kb)

Supplementary Fig. 2

Locations of DALgenes (red) in species lacking the DAL cluster. (PDF 421 kb)

Supplementary Fig. 3

Phylogenetic trees of Dal4/Fur4 and Dal7/Mls1 sequences. (PDF 40 kb)

Supplementary Fig. 4

The DAL cluster is a meiotic recombination coldspot. (PDF 30 kb)

Supplementary Table 1

Sequence evolution in DAL genes. (PDF 68 kb)

Supplementary Note (PDF 48 kb)

Supplementary Methods (PDF 55 kb)

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Wong, S., Wolfe, K. Birth of a metabolic gene cluster in yeast by adaptive gene relocation. Nat Genet 37, 777–782 (2005).

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