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Co-evolution of transcriptional and post-translational cell-cycle regulation


DNA microarray studies have shown that hundreds of genes are transcribed periodically during the mitotic cell cycle of humans1, budding yeast2,3, fission yeast4,5,6 and the plant Arabidopsis thaliana7. Here we show that despite the fact the protein complexes involved in this process are largely the same among all eukaryotes, their regulation has evolved considerably. Our comparative analysis of several large-scale data sets reveals that although the regulated subunits of each protein complex are expressed just before its time of action, the identity of the periodically expressed proteins differs significantly between organisms. Moreover, we show that these changes in transcriptional regulation have co-evolved with post-translational control independently in several lineages; loss or gain of cell-cycle-regulated transcription of specific genes is often mirrored by changes in phosphorylation of the proteins that they encode. Our results indicate that many different solutions have evolved for assembling the same molecular machines at the right time during the cell cycle, involving both transcriptional and post-translational layers that jointly control the dynamics of biological systems.

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Figure 1: Periodic expression is poorly conserved.
Figure 2: Protein complexes are regulated through different subunits in each organism.
Figure 3: Cyclin-dependent kinases preferentially phosphorylate dynamic proteins.


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We thank C. von Mering for assistance with detection of orthologues, and P. Nurse, E. Karsenti, J. Bähler, and members of the Bork and Brunak groups for comments on the manuscript. This work was supported by grants from the Danish National Research Foundation, the Danish Technical Research Council, and the European Commission FP6 Programme (grants DIAMONDS and BioSapiens).

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Supplementary Notes

Supplementary Methods and Supplementary Results. This file provides a detailed material and methods section as well as additional results. In particular, the results for numerous protein complexes are described and compared to current knowledge. (PDF 1182 kb)

Supplementary Notes

Archive of the supplementary web site. This file contains a complete copy of all information on the supplementary web site ( To use, unpack the zip file and open the file README.html in a web browser. (ZIP 1203 kb)

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Jensen, L., Jensen, T., de Lichtenberg, U. et al. Co-evolution of transcriptional and post-translational cell-cycle regulation. Nature 443, 594–597 (2006).

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