Evolution of protein-protein interactions

A recent report of interest:


The abstract:

Highly specific interactions between proteins are a fundamental prerequisite for life, but how they evolve remains an unsolved problem. In particular, interactions between initially unrelated proteins require that they evolve matching surfaces. It is unclear whether such surface compatibilities can only be built by selection in small incremental steps, or whether they can also emerge fortuitously. Here, we used molecular phylogenetics, ancestral sequence reconstruction and biophysical characterization of resurrected proteins to retrace the evolution of an allosteric interaction between two proteins that act in the cyanobacterial photoprotection system. We show that this interaction between the orange carotenoid protein (OCP) and its unrelated regulator, the fluorescence recovery protein (FRP), evolved when a precursor of FRP was horizontally acquired by cyanobacteria. FRP’s precursors could already interact with and regulate OCP even before these proteins first encountered each other in an ancestral cyanobacterium. The OCP–FRP interaction exploits an ancient dimer interface in OCP, which also predates the recruitment of FRP into the photoprotection system. Together, our work shows how evolution can fashion complex regulatory systems easily out of pre-existing components.

There has been some recent (sorry, no links) interest in the ID community regarding the vastness and complexity of the protein interaction network. This study throws cold water on the notion that the formation and evolution of these networks must be beyond the reach of “unguided” processes.


The specific compatibility of the FRPL from the Desulfobacteraceae species with cyanobacterial OCPs is entirely accidental, because this protein evolved in a genome that contains no OCP. This proves that highly complementary protein surfaces can evolve completely by chance, and that such initially accidental interactions can become incorporated into the biology of organisms. Our work thus raises the possibility that some or even many protein–protein interactions are initially created without the action of direct natural selection. Organisms may in fact be bombarded with virtually fully formed interactions that are created when horizontal transfer, changes in cellular localization or spatiotemporal expression patterns bring together proteins with fortuitously compatible surfaces. From this pool, natural selection would then purge those that are harmful, fix those that are useful and ignore those that are harmless.

Probably not all that less likely than finding two stones with roughly matching surfaces on a beach. We already know a long-term trend in protein evolution is selection against aggregation propensity. Proteins naturally tend to stick to each other, and many are flexible and can bend to accommodate different binding partners. Heck, there are even cases where some proteins when expressed in different species can be toxic, because they just by chance has this property of having a surface area that matches with high affinity to one or more other proteins, and this can interfere with their functions.