Historical Contingency: Insights from in-vivo Molecular Evolution of a Reconstructed Ancient Protein
Living organisms have a vast genetic heritage that shapes their future ability to adapt. Living organisms may therefore be viewed as both benefiting from and trapped by their evolutionary history. Two experimental approaches, ancestral sequence reconstruction and experimental evolution with microorganisms, can be used to provide valuable insights into the mutational steps that constitute an organism’s genetic heritage. Ancestral sequence reconstruction follows a backwards-from-present-day strategy in which various ancestral forms of a modern gene or protein are reconstructed and then studied mechanistically. Experimental evolution, by contrast, follows a forward-from-present day strategy in which microbial populations are evolved in the laboratory under defined conditions in which their evolutionary paths may be closely monitored. Here I describe a novel hybrid of these two methods, in which synthetic components constructed from inferred ancestral gene or protein sequences are placed into the genomes of modern organisms that are then experimentally evolved. Replacing an essential bacterial gene with its ancient counterpart initiated a struggle for existence in these microbial populations since the ancient gene is maladapted to modern environments. Observing the real-time evolution of these resurrected genes as they adapt to the conditions of modern bacteria therefore allowed us to monitor evolution in action. Through this system, we aim to understand how the modern components of a cellular system would co-function with their ancestral interaction partners, if given a chance. This approach to evolutionary synthetic biology provides a new way to examine historical aspects of evolution, namely the respective roles that chance, necessity, and historical contingency play in organismal evolution.
The goal of BETÜL KACAR’s research is to expand our understanding of the molecular mechanisms that lead to evolutionary innovations. Her approach has been to experimentally examine the relationship between historical constraints and evolutionary trajectories at protein, protein-protein interaction network and system levels. Specifically, she combines experimental evolution with ancestral sequence reconstruction, whereby ancient protein sequences inferred through phylogeny are inserted and expressed within extant microorganisms. The microorganisms are then monitored as the resurrected molecules adapt within the host population under laboratory conditions. Through this synthesis of synthetic biology, biochemistry, and experimental evolution she aims to generate a new understanding of the functional, structural and historical constraints that shape biological evolution. Betül Kacar received her doctoral training in biomolecular chemistry, and is currently conducting her research as a Postdoctoral Fellow through the NASA Astrobiology Institute.