Selection maintains signaling function of a highly diverged intrinsically disordered region.
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 inSaccharomyces cerevisiaethat 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 inS. cerevisiaeWe 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.
Department of Cell and Systems Biology, University of Toronto, Toronto, ON, Canada, M5S 3G5.
Taraneh
T
Zarin
Department of Ecology and Evolutionary Biology, University of Toronto, Toronto, ON, Canada, M5S 3B2.
Caressa N
CN
Tsai
Faculty of Arts and Sciences Center for Systems Biology, Harvard University, Cambridge, MA 02138.
Alex N
AN
Nguyen Ba
Department of Cell and Systems Biology, University of Toronto, Toronto, ON, Canada, M5S 3G5; alan.moses@utoronto.ca.|Department of Ecology and Evolutionary Biology, University of Toronto, Toronto, ON, Canada, M5S 3B2.
Alan M
AM
Moses
D000595:Amino Acid Sequence; D064267:Intrinsically Disordered Proteins / Q000378:metabolism*; D010802:Phylogeny; D011487:Protein Conformation; D020543:Proteome / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology
D064267:Intrinsically Disordered Proteins; D020543:Proteome
evolution; intrinsically disordered; phylogenetic comparative method; quantitative trait; stabilizing selection