Protein interaction evolution from promiscuity to specificity with reduced flexibility in an increasingly complex network

Abstract

A key question regarding protein evolution is how proteins adapt to the dynamic environment in which they function and how in turn their evolution shapes the protein interaction network. We used extant and resurrected ancestral plant MADS-domain transcription factors to understand how SEPALLATA3, a protein with hub and glue properties, evolved and takes part in network organization. Although the density of dimeric interactions was saturated in the network, many new interactions became mediated by SEPALLATA3 after a whole genome triplication event. By swapping SEPALLATA3 and its ancestors between dimeric networks of different ages, we found that the protein lost the capacity of promiscuous interaction and acquired specificity in evolution. This was accompanied with constraints on conformations through proline residue accumulation, which made the protein less flexible. SHORT VEGETATIVE PHASE on the other hand (non-hub) was able to gain protein-protein interactions due to a C-terminal domain insertion, allowing for a larger interaction interface. These findings illustrate that protein interaction evolution occurs at the level of conformational dynamics, when the binding mechanism concerns an induced fit or conformational selection. Proteins can evolve towards increased specificity with reduced flexibility when the complexity of the protein interaction network requires specificity.

Gene duplication and relaxation from selective constraints of GCYC genes correlated with various floral symmetry patterns in Asiatic Gesneriaceae tribe Trichosporeae

“…In MADS-box gene family of angiosperms, multiple gene duplications have provided evolutionary flexibility allowing each copy to be randomly fixed to maintain its original function or acquired new roles to interact with other copies or downstream genes [75, 76]. Indeed, protein interactions exist among the CYC / TB1 gene subfamily of TCP family, demonstrated that combinations of different CYC copies may interact each other to generate novel genetic modules, such as those reported in Arabidopsis and tomato [77, 78].…”

Real Talk: The Inter-play Between the mTOR, AMPK, and Hexosamine Biosynthetic Pathways in Cell Signaling

“…In some cases, it would be more accurate to consider these proteins as competing signals. Partly, this arrangement is likely the byproduct of evolution, and the mechanism through which new functions can be introduced (i.e., evolution works with what is already there, so new proteins will have similar binding domains to previous domains, especially early on) ( 62 , 63 ). Thus, a more specific protein may have to compete with a large number of less specific alternatives.…”

Evolutionary variation in MADS-box dimerization affects floral development and protein stability

“…Very few MADS-box protein-protein interactions have been examined in a comparative framework. However, given evolutionary variation in interactions between B-class proteins (the least promiscuous of the floral MADS-box proteins); the propensity for rapid evolution of MADS-box protein-protein interactions; and many lineage-specific MADS-box gene duplications, MADS-box protein-protein interactions profiles are likely diverse within populations and species (18,(42)(43)(44)(45). This cryptic molecular diversity may contribute to the overall evolvability of floral morphology; when genetic variation can accumulate in a system, without consequent phenotypic change, the system itself can be more evolvable (46).…”