The catalytic origin of modern molecular functions inferred from phylogenomic analysis of ontological data

A paper by Kyung Mo Kim and Gustavo Caetano-Anollés appeared published today in Molecular Biology and Evolution (27: 1710-1733, 2010) that describes the origin and evolution of molecular functions in biology.

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 [1]. They provide direct insight into the emergence, development, and organization of cellular life. However, molecular functions make up a network-like hierarchy of relationships that tell little of evolutionary links between structure and function. For example, Gene Ontology terms represent widely used vocabularies of processes and functions with evolutionary relationships that are implicit but not defined [2]. This new publication uncovers patterns of global evolutionary history in ontological terms associated with the sequence of 38 genomes. These patterns unfold the metabolic origins of molecular functions and major biological transitions that are evident in the evolutionary progression toward complex life [3]. Phylogenies reveal the primordial appearance of hydrolases, transferases, and other enzymatic activities, indicating 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. ATPase, GTPase, and helicase activities were the most ancient molecular functions at lower hierarchical levels of ontological complexity. Furthermore, the history of biological processes showed that cellular biopolymer metabolic processes preceded biopolymer biosynthesis and essential processes related to macromolecular formation, energy generation, and signaling.

The phylogenomic approach that is described takes the structure and function paradigm to a completely new level of abstraction, demonstrating a ‘metabolic first’ origin of life and the progressive development of protein biosynthetic machinery, transport systems, and regulation. The fact that chemosynthesis precedes biosynthesis is remarkable and challenges the existence of an ancient RNA world [4]. Phylogenetic statements are reliable, especially because they are congruent with progressive evolutionary change and phylogenomic inferences derived from protein structure [5]. Ultimately, the procedure uncovers patterns in the morphing of function that are unprecedented and necessary for systematic views in biology.

1.     Darwin, C.R. 1859. On the origin of species by means of natural selection. Murray, London.

2.     Ashburner, M., Ball, C.A., Blake, J.A. et al. 2000. Gene Ontology: tool for the unification of biology. Nat Genet 25:25-29.

3.     Szathmáry, E., Maynard Smith, J. 1995. The major evolutionary transitions. Nature 374: 227-232.

4.     Gesteland, R.F., Atkins, J.F. 1993. The RNA world. Cold Spring Harbor press, New York.

5.    Caetano-Anollés, G., Kim, H.S., Mittenthal, J.E. 2007. The origin of modern metabolic networks inferred from phylogenomic analysis of protein architecture. Proc Natl Acad Sci USA 104:9358-9363.