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Adaptive mutations that prevent cross-talk 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 cross-talk with a paralogous pathway that arose specifically in α-proteobacteria. Our findings demonstrate that duplication and the subsequent need to avoid cross-talk strongly influence signaling protein evolution. These results provide a concrete example of how system-wide insulation can be achieved post-duplication through a surprisingly limited number of mutations. Our work may help explain the apparent ease with which paralogous protein families expanded in all organisms.

ORGANISM(S): Caulobacter vibrioides NA1000

PROVIDER: GSE37545 | GEO | 2012/07/02

SECONDARY ACCESSION(S): PRJNA161859

REPOSITORIES: GEO

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Adaptive mutations that prevent cross-talk enable the expansion of paralogous signaling protein families

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