Modern metabolism as a palimpsest of the RNA world.

Abstract

An approach is developed for constructing models of ancient organisms using data from metabolic pathways, genetic organization, chemical structure, and enzymatic reaction mechanisms found in contemporary organisms. This approach is illustrated by a partial reconstruction of a model for the "breakthrough organism," the last organism to use RNA as the sole genetically encoded biological catalyst. As reconstructed here, this organism had a complex metabolism that included dehydrogenations, transmethylations, carboncarbon bond-forming reactions, and an energy metabolism based on phosphate esters. Furthermore, the breakthrough organism probably used DNA to store genetic information, biosynthesized porphyrins, and used terpenes as its major lipid component. This model differs significandy from prevailing models based primarily on genetic data.Since the discovery of self-splicing RNA (1), molecular biology has become the central focus of speculation concerning early forms of life. Many of these speculations consider genetic structure to the exclusion of most other biochemical data in modeling the "RNA world" (2-5). As discussed elsewhere, this narrow focus leads to interesting but often chemically and biologically implausible models (6-10).We develop here an alternative approach for generating experimentally testable models of the RNA world, based on metabolic, structural, and mechanistic data from contemporary organisms. Several specific "paradigms," problem solutions covering individual topics in biochemical evolution, are constructed by this approach. These paradigms demonstrate the utility of this broader view and provide elements of a framework for interpreting the "historical" component of modern biochemistry (11).We begin by assuming that life on earth passed through three episodes ( Fig. 1) (12). In the first (the RNA world) (13), RNA was the only genetically encoded component of biological catalysts. The second episode began with the invention of translation-based synthesis of proteins in a "breakthrough organism," the first organism to contain a genetically encoded messenger RNA that directed the synthesis of a protein selectable for its catalytic activity. The third episode comprises the divergent evolution of the "progenote," the most recent common ancestor of all modern forms of life.a This model views modern macromolecular catalysis as a "palimpsest" of an earlier metabolic state, with features that arose recently ("derived traits") superimposed upon features that are remnants of ancient life ("primitive traits"). (A palimpsest is a parchment that has been inscribed two or more times, with the previous texts imperfectly erased and therefore still partially legible.) To describe the biochemistry of these ancient organisms, we must first examine contemporary biochemical traits to distinguish ancient information from information added later. These descriptions are prerequisites for descriptions ofthe development ofmetabolism, the origin of translation, and other events that occurred in the RNA world....

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The origin of modern metabolic networks inferred from phylogenomic analysis of protein architecture

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Self-Incorporation of coenzymes by ribozymes

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