Experimental evolution of protein–protein interaction networks

Abstract

The modern synthesis of evolutionary theory and genetics has enabled us to discover underlying molecular mechanisms of organismal evolution. We know that in order to maximize an organism's fitness in a particular environment, individual interactions among components of protein and nucleic acid networks need to be optimized by natural selection, or sometimes through random processes, as the organism responds to changes and/or challenges in the environment. Despite the significant role of molecular networks in determining an organism's adaptation to its environment, we still do not know how such inter- and intra-molecular interactions within networks change over time and contribute to an organism's evolvability while maintaining overall network functions. One way to address this challenge is to identify connections between molecular networks and their host organisms, to manipulate these connections, and then attempt to understand how such perturbations influence molecular dynamics of the network and thus influence evolutionary paths and organismal fitness. In the present review, we discuss how integrating evolutionary history with experimental systems that combine tools drawn from molecular evolution, synthetic biology and biochemistry allow us to identify the underlying mechanisms of organismal evolution, particularly from the perspective of protein interaction networks.

Experimental Evolution of Escherichia coli Harboring an Ancient Translation Protein

“…Considering the important role of EF-Tu in the translational machinery, mutations accumulating directly on the EF-Tu gene can cause cell lethality and thus may not be readily adaptive (Goldman et al 2010; Kacar and Gaucher 2013; Pereira-Leal et al 2006). On the other hand, there are likely to be beneficial mutations that can occur without causing cell lethality, but they do not confer the advantage that others do under the same conditions, resulting in tuf mutations always being outcompeted within earlier generations.…”

“…Mathematical sequence reconstructions of ancient genes and their subsequent in vitro biochemical characterization alone, however, may not necessarily provide the salient details of why the protein evolved along a particular evolutionary pathway (Bar-Rogovsky et al 2015; Copley 2012; Dean and Thornton 2007; Kacar 2016; Zhu et al 2005). Incorporating a functional perspective into the study of ancient proteins was suggested to be instrumental for understanding historical adaptive pathways as well as bridging the evolution of protein-level function and the organism-level behavior, thus enabling predictions that connect inferred genotype to ancestral phenotype (Dean and Thornton 2007; Harms and Thornton 2013; Kacar and Gaucher 2013, 2012; Lunzer et al 2005; Zhu et al 2005). …”

In silico identification of essential proteins in Corynebacterium pseudotuberculosis based on protein-protein interaction networks

“…Nodes with a high node degree are called hubs, but a clear definition of what node degree should be regarded as “high” is missing [103]. Nevertheless, identifying nodes with a larger degree is a means for identifying essential proteins [104–106], since the knockout of hub proteins most likely cause a substantial disruption in the interaction network [85]. We decided to classify proteins as essential when they are among the top 15 % proteins with respect to the node degree, a threshold commonly used [103].…”

Experimental evolution of Escherichia coli harboring an ancient translation protein

“…Considering the important role of EF-Tu in the translational machinery, mutations accumulating directly on the EF-Tu gene can cause cell lethality and thus may not be readily adaptive (Goldman et al 2010;Kacar and Gaucher 2013;Pereira-Leal et al 2006). On the other hand, there are likely to be beneficial mutations that can occur without causing cell lethality, but they do not confer the advantage that others do under the same conditions, resulting in tuf mutations always being outcompeted within earlier generations.…”