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Science 10 August 2007:
Vol. 317. no. 5839, pp. 815 - 819
DOI: 10.1126/science.1140748
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Reports

Divergence of Transcription Factor Binding Sites Across Related Yeast Species

Anthony R. Borneman,1* Tara A. Gianoulis,2 Zhengdong D. Zhang,3 Haiyuan Yu,3 Joel Rozowsky,3 Michael R. Seringhaus,3 Lu Yong Wang,4 Mark Gerstein,2,3,5 Michael Snyder1,2,3{dagger}

Characterization of interspecies differences in gene regulation is crucial for understanding the molecular basis of both phenotypic diversity and evolution. By means of chromatin immunoprecipitation and DNA microarray analysis, the divergence in the binding sites of the pseudohyphal regulators Ste12 and Tec1 was determined in the yeasts Saccharomyces cerevisiae, S. mikatae, and S. bayanus under pseudohyphal conditions. We have shown that most of these sites have diverged across these species, far exceeding the interspecies variation in orthologous genes. A group of Ste12 targets was shown to be bound only in S. mikatae and S. bayanus under pseudohyphal conditions. Many of these genes are targets of Ste12 during mating in S. cerevisiae, indicating that specialization between the two pathways has occurred in this species. Transcription factor binding sites have therefore diverged substantially faster than ortholog content. Thus, gene regulation resulting from transcription factor binding is likely to be a major cause of divergence between related species.

1 Department of Molecular, Cellular and Developmental Biology, Yale University, New Haven, CT 06511, USA.
2 Program in Computational Biology, Yale University, New Haven, CT 06511, USA.
3 Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06511, USA.
4 Integrated Data Systems Department, Siemens Corporate Research, Princeton, NJ 08540, USA.
5 Department of Computer Science, Yale University, New Haven, CT 06511, USA.

* Present address: Australian Wine Research Institute, Glen Osmond, Adelaide, SA 5064, Australia.

{dagger} To whom correspondence should be addressed. E-mail: michael.snyder{at}yale.edu

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Science. ISSN 0036-8075 (print), 1095-9203 (online)