Evolutionary dynamics of membrane transporters and channels: enhancing function through fusion

The formation of complex multidomain proteins has occurred many times during evolution. For enzymes, this often confers the addition of new functions or new routes to regulate function. Herein we review how this same process has impacted on the function of membrane transporters and channels, proteins that, due to their integral membrane location, are potentially more constrained in the fusions they can accommodate. Using examples primarily from bacterial systems, we illustrate diverse instances of functional fusions and find evidence for promiscuous fusion partners that have fused to many different classes of membrane protein. We consider the evidence that topology and stoichiometry issues might limit the range of fusions that are selected in nature and attempt to find examples where a functional benefit of direct fusion over split proteins has been demonstrated. Finally, we consider whether the reverse process of gene fission has been important in membrane transporter evolution.