Emergence and Evolution of Modern Molecular Functions Inferred from Phylogenomic Analysis of Ontological Data

Abstract

The biological processes that characterize the phenotypes of a living system are embodied in the function of molecules and hold the key to evolutionary history, delimiting natural selection and change. These processes and functions provide direct insight into the emergence, development, and organization of cellular life. However, detailed molecular functions make up a network-like hierarchy of relationships that tells little of evolutionary links between structure and function in biology. For example, Gene Ontology terms represent widely-used vocabularies of processes and functions with evolutionary relationships that are implicit but not defined. Here, we uncover patterns of global evolutionary history in ontological terms associated with the sequence of 38 genomes. These patterns unfold the metabolic origins of modern molecular functions and major biological transitions in evolution toward complex life. Phylogenies reveal the primordial appearance of hydrolases and transferases, with ATPase, GTPase, and helicase activities being the most ancient. This indicates that ancient catalysts were crucial for binding and transport, the emergence of nucleic acids and protein biopolymers, and the communication of primordial cells with the environment. Finally, the history of biological processes showed that cellular biopolymer metabolic processes preceded biopolymer biosynthesis and essential processes related to macromolecular formation, directly challenging the existence of an RNA world. Phylogenomic systematization of biological function takes the structure and function paradigm to a completely new level of abstraction, demonstrating a "metabolic first" origin of life. The approach uncovers patterns in the morphing of function that are unprecedented and necessary for systematic views in biology.