title: Adaptive mutations that prevent crosstalk enable the expansion of paralogous signaling protein families.
abstract: Orthologous proteins often harbor numerous substitutions, but whether these differences result from neutral or adaptive processes is usually unclear. To tackle this challenge, we examined the divergent evolution of a model bacterial signaling pathway comprising the kinase PhoR and its cognate substrate PhoB. We show that the specificity-determining residues of these proteins are typically under purifying selection but have, in α-proteobacteria, undergone a burst of diversification followed by extended stasis. By reversing mutations that accumulated in an α-proteobacterial PhoR, we demonstrate that these substitutions were adaptive, enabling PhoR to avoid crosstalk with a paralogous pathway that arose specifically in α-proteobacteria. Our findings demonstrate that duplication and the subsequent need to avoid crosstalk strongly influence signaling protein evolution. These results provide a concrete example of how system-wide insulation can be achieved postduplication through a surprisingly limited number of mutations. Our work may help explain the apparent ease with which paralogous protein families expanded in all organisms.
authors: Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
authors: Emily J
authors: EJ
authors: Capra
authors: Barrett S
authors: BS
authors: Perchuk
authors: Jeffrey M
authors: JM
authors: Skerker
authors: Michael T
authors: MT
authors: Laub
mesh_terms: D020561:Alphaproteobacteria / Q000235:genetics* / Q000378:metabolism*; D001426:Bacterial Proteins / Q000235:genetics*; D019143:Evolution, Molecular; D009154:Mutation; D010802:Phylogeny; D012641:Selection, Genetic; D015398:Signal Transduction
chemical_list: D001426:Bacterial Proteins; C061279:PhoR protein, Bacteria