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.

中文翻译：

---

膜转运蛋白和通道的进化动力学：通过融合增强功能。

复杂的多域蛋白的形成在进化过程中已经发生了很多次。对于酶，这通常赋予新功能或调节功能的新途径。本文中，我们回顾了相同的过程如何影响膜转运蛋白和通道的功能，由于其整体的膜位置，蛋白质可能更受其可容纳融合蛋白的限制。使用主要来自细菌系统的示例，我们说明了功能融合的各种情况，并找到了已经融合到许多不同类别的膜蛋白上的混杂融合伴侣的证据。我们考虑了拓扑和化学计量学问题可能会限制自然选择的融合范围的证据，并尝试寻找已证明直接融合优于分裂蛋白的功能优势的实例。最后，我们考虑基因分裂的反向过程是否对膜转运蛋白的进化很重要。