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Proc Natl Acad Sci U S A. 2017 Feb 21;114(8):E1450-E1459. doi: 10.1073/pnas.1614787114. Epub 2017 Feb 6.

Selection maintains signaling function of a highly diverged intrinsically disordered region.

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Department of Cell and Systems Biology, University of Toronto, Toronto, ON, Canada, M5S 3G5.
Department of Ecology and Evolutionary Biology, University of Toronto, Toronto, ON, Canada, M5S 3B2.
Faculty of Arts and Sciences Center for Systems Biology, Harvard University, Cambridge, MA 02138.
Department of Cell and Systems Biology, University of Toronto, Toronto, ON, Canada, M5S 3G5;


Intrinsically disordered regions (IDRs) are characterized by their lack of stable secondary or tertiary structure and comprise a large part of the eukaryotic proteome. Although these regions play a variety of signaling and regulatory roles, they appear to be rapidly evolving at the primary sequence level. To understand the functional implications of this rapid evolution, we focused on a highly diverged IDR in Saccharomyces cerevisiae that is involved in regulating multiple conserved MAPK pathways. We hypothesized that under stabilizing selection, the functional output of orthologous IDRs could be maintained, such that diverse genotypes could lead to similar function and fitness. Consistent with the stabilizing selection hypothesis, we find that diverged, orthologous IDRs can mostly recapitulate wild-type function and fitness in S. cerevisiae We also find that the electrostatic charge of the IDR is correlated with signaling output and, using phylogenetic comparative methods, find evidence for selection maintaining this quantitative molecular trait despite underlying genotypic divergence.


evolution; intrinsically disordered; phylogenetic comparative method; quantitative trait; stabilizing selection

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