Beyond Metabolism and Genetics

A “metabolism-first” approach to life is one where life is understood as the evolution of biochemical reactions. It contrasts with “genetics-first” approaches which focus on the emergence of genetic polymers as the first living entities. Both approaches face conceptual problems, prompting arguments advocating that the community must synthesize the two to understand the emergence of life. Here, we discuss how the emergence of chiral asymmetry provides a unique lens into this union. Biomolecular chirality is predominantly discussed within genetics-first approaches to explain the homochirality of biopolymers such as RNA, DNA and proteins. However, asymmetrical chiral reactions are found across all three domains of life involving biopolymers and other small molecules associated with metabolism. This suggests the Last Universal Common Ancestor (LUCA) contained asymmetrically chiral reactions, and those reactions have persevered throughout evolutionary time. In this work, we explore the impact of chirality over the history of life using network expansion, an algorithm where a set of initial compounds (the seed set) are introduced to a reaction network, then reacted together to determine the influence of the seed set on the network. The role of these seed sets on the expansion of chirality is determined by the size and overall chiral makeup of the expanded networks, providing clues to the emergence of chirality as a network-level property of biochemistry. We present results of this analysis and discuss how it permits a conceptual reframing of chirality that unifies metabolism-first approaches with characteristics of nascent life previously discussed only in genetics-first approaches.