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Gene duplication and the adaptive evolution of a classic genetic switch

Abstract

How gene duplication and divergence contribute to genetic novelty and adaptation has been of intense interest, but experimental evidence has been limited. The genetic switch controlling the yeast galactose use pathway includes two paralogous genes in Saccharomyces cerevisiae that encode a co-inducer (GAL3) and a galactokinase (GAL1). These paralogues arose from a single bifunctional ancestral gene as is still present in Kluyveromyces lactis. To determine which evolutionary processes shaped the evolution of the two paralogues, here we assess the effects of precise replacement of coding and non-coding sequences on organismal fitness. We suggest that duplication of the ancestral bifunctional gene allowed for the resolution of an adaptive conflict between the transcriptional regulation of the two gene functions. After duplication, previously disfavoured binding site configurations evolved that divided the regulation of the ancestral gene into two specialized genes, one of which ultimately became one of the most tightly regulated genes in the genome.

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Figure 1: GAL3 + encodes the best co-inducer.
Figure 2: Most adaptive divergence between GAL1 and GAL3 occurred in the promoters.
Figure 3: Adaptive conflict in the configuration of Gal4 binding sites.
Figure 4: Model of the evolution of the GAL genetic switch.

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Acknowledgements

We thank B. L. Williams for sharing unpublished data, reagents and the competition assay; J. E. Selegue for technical support; M. Johnston and Washington University in St Louis for access to laboratory space and equipment; Collection de Levures d'Intérêt Biotechnologique for K. lactis strain CLIB210; H. Y. Steensma for the NHEJ-deficient K. lactis strain and transformation protocol; J. H. Hegemann for the kanMX cassette; B. L. Williams, P. M. van Wynsberghe and Carroll laboratory members for technical advice; L. M. Olds for artwork; and B. L. Williams, B. Prud’homme and M. Johnston for critical reading of the manuscript. The Howard Hughes Medical Institute supported this work through an investigatorship (S.B.C.) and predoctoral fellowship (C.T.H.).

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Correspondence to Sean B. Carroll.

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The file contains Supplementary Discussion of Supplementary Tables S1-S4, Supplementary Tables S1-S4, Supplementary Figure S1 with Legend and additional references. (PDF 391 kb)

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Hittinger, C., Carroll, S. Gene duplication and the adaptive evolution of a classic genetic switch. Nature 449, 677–681 (2007). https://doi.org/10.1038/nature06151

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