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Evolution of alternative transcriptional circuits with identical logic

Nature volume 443, pages 415–420 (2006)Cite this article

Abstract

Evolution of gene regulation is an important contributor to the variety of life. Here, we analyse the evolution of a combinatorial transcriptional circuit composed of sequence-specific DNA-binding proteins that are conserved among all eukaryotes. This circuit regulates mating in the ascomycete yeast lineage. We first identify a group of mating genes that was transcriptionally regulated by an activator in a fungal ancestor, but is now transcriptionally regulated by a repressor in modern bakers' yeast. Despite this change in regulatory mechanism, the logical output of the overall circuit remains the same. By examining the regulation of mating in modern yeasts that are related to different extents, we deduce specific, sequential changes in both cis- and trans-regulatory elements that constitute the transition from positive to negative regulation. These changes indicate specific mechanisms by which fitness barriers were traversed during the transition.

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Figure 1: a-type mating is negatively regulated in modern S. cerevisiae , but was positively regulated in its ancestor.
Figure 2: Identification of a-specific genes in C. albicans.
Figure 3: Identification and validation of the C. albicans asg operator.
Figure 4: Analysis of cis - asg regulation across species.
Figure 5: Evolution of the α2–Mcm1 interaction.
Figure 6: Ordering the changes in cis - and trans -regulatory elements.

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Acknowledgements

We are grateful to M. Jacobson for advice provided in modelling the K. lactis α2 and Mcm1 structures. We also thank S. Ästrøm for providing unpublished K. lactis strains and advice on their handling, P. Sudbury for providing the GFP reporter construct, M. Lorentz and G. Fink for the collaboration that produced the DNA microarrays used in this paper, and the Broad Institute (http://www.broad.mit.edu/annotation/fungi/fgi/), the Sanger Center (http://www.sanger.ac.uk/Projects/Fungi/), and the Pathogen Sequencing Unit at the Wellcome Trust Sanger Institute (http://www.sanger.ac.uk/sequencing/Candida/dubliniensis/) for making sequence data available. M. Ptashne provided valuable comments on the manuscript. We thank B. Hromatka for overseeing microarray printing, and R. Bennett for microarray data and discussions. R. Zordan, A. Uhl, M. Lohse, M. Miller, R. Wu, C. Chaivorapol and other members of the Johnson and Li labs provided useful discussions. This work was supported by grants from the NIH to A.D.J. A.E.T was supported by a Howard Hughes Medical Institute Predoctoral Fellowship. B.B.T. is an NSF Predoctoral Fellow. B.B.T. and H.L. acknowledge partial support from a Packard Fellowship in Science and Engineering (to H.L.) and an NIH grant. Author Contributions A.E.T. determined the asgs of C. albicans, and validated the asg operator site. B.T. constructed the phylogenetic tree, analysed asg operators across multiple species, and modelled the K. lactis α2–Mcm1 interaction. H.L. and A.D.J. oversaw the work.

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Author notes

  1. Annie E. Tsong

    Present address: Department of Molecular and Cell Biology, University of California Berkeley, Lawrence Berkeley National Labs, 1 Cyclotron Road, Mailstop 84-355, Berkeley, California, 94703, USA

  2. Annie E. Tsong and Brian B. Tuch: *These authors contributed equally to this work

Authors and Affiliations

  1. Department of Biochemistry & Biophysics,

    Annie E. Tsong, Brian B. Tuch, Hao Li & Alexander D. Johnson

  2. Department of Microbiology & Immunology, University of California San Francisco, San Francisco, California, 94143-2200, USA

    Annie E. Tsong, Brian B. Tuch & Alexander D. Johnson

  3. Immunology, University of California San Francisco,

    Annie E. Tsong, Brian B. Tuch & Alexander D. Johnson

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  1. Annie E. Tsong
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  4. Alexander D. Johnson
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Corresponding author

Correspondence to Alexander D. Johnson.

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Competing interests

Microarray data are available in Supplementary Information and at http://genome.ucsf.edu/asg_evolution/. Reprints and permissions information is available at www.nature.com/reprints. The authors declare no competing financial interests.

Supplementary information

Supplementary Notes

This file contains Supplementary Methods, Supplementary Figure Legends and Supplementary Tables (Position weight matrices for C. albicans and S. cerevisiae asg operators). (DOC 118 kb)

Supplementary Figure 1

Strategy used to identify asgs in C. albicans. (PDF 21 kb)

Supplementary Figure 2

Clustering analysis of putative asg operators (JPG 105 kb)

Supplementary Data

Microarray data used to identify the asgs in C. albicans (DOC 23 kb)

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Tsong, A., Tuch, B., Li, H. et al. Evolution of alternative transcriptional circuits with identical logic. Nature 443, 415–420 (2006). https://doi.org/10.1038/nature05099

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