The Coevolutionary Roots of Biochemistry and Cellular Organization Challenge the RNA World Paradigm

Abstract

The origin and evolution of modern biochemistry and cellular structure is a complex problem that has puzzled scientists for almost a century. While comparative, functional and structural genomics has unraveled considerable complexity at the molecular level, there is very little understanding of the origin, evolution and structure of the molecules responsible for cellular or viral features in life. Recent efforts, however, have dissected the emergence of the very early molecules that populated primordial cells. Deep historical signal was retrieved from a census of molecular structures and functions in thousands of nucleic acid and protein structures and hundreds of genomes using powerful phylogenomic methods. Together with structural, chemical and cell biology considerations, this information reveals that modern biochemistry is the result of the gradual evolutionary appearance and accretion of molecular parts and molecules. These patterns comply with the principle of continuity and lead to molecular and cellular complexity. Here, we review findings and report possible origins of molecular and cellular structure, the early rise of lipid biosynthetic pathways and components of cytoskeletal microstructures, the piecemeal accumulation of domains in ATP synthase complexes and the origin and evolution of the ribosome. Phylogenomic studies suggest the last universal common ancestor of life, the ‘urancestor', had already developed complex cellular structure and bioenergetics. Remarkably, our findings falsify the existence of an ancient RNA world. Instead they are compatible with gradually coevolving nucleic acids and proteins in interaction with increasingly complex cofactors, lipid membrane structures and other cellular components. This changes the perception we have of the rise of modern biochemistry and prompts further analysis of the emergence of biological complexity in an ever-expanding coevolving world of macromolecules.

Piecemeal Buildup of the Genetic Code, Ribosomes, and Genomes from Primordial tRNA Building Blocks

“…We note that in most cases the recruited parts become physically associated with the growing system, with b of Equation (2) representing the growing system and a the accreted part. Examples of accretion of these kinds are macromolecular complexes such as the ATP synthases and the ribosome [25,26]. The F-type and A/V-type synthases are multi-subunit complexes responsible for membrane-coupled energy conversion reactions.…”

Archaea: The First Domain of Diversified Life

“… Figure 2, for example, shows a phylogenomic model of ribosomal molecular accretion derived from the survey of protein domain structures in genomes and substructures in rRNA molecules. The accretion process of component parts of the universal core appears to have been a painstakingly slow process that unfolded during a period of ~2 billion years and overlapped with the first episodes of organismal diversification [30]. Despite of this complexity, the focus of biodiversity studies was for decades the small subunit rRNA molecule [31].…”

The natural history of transfer RNA and its interactions with the ribosome

“…In our case, the evolving trait is the gradual accumulation of domains in proteomes and the semipunctuated discovery of new fold structures (made evident for example in simulations; Zeldovich et al, 2007). The predictive power of ToDs is considerable (Caetano-Anollés and Seufferheld, 2013) and central for the history of tRNA, as ToDs have established the evolutionary history of aaRS domain structures and their associated coevolving tRNA molecules (Caetano-Anollés et al, 2013). The timeline of evolutionary appearance of fold families revealed the early emergence of the “operational” RNA code linked to the specificities of synthetases that were homologous to the catalytic domains of modern TyrRS and SerRS protein enzymes.…”

“…Discrimination mediated by aaRSs and EFs against misincorporated tRNA and amino acids is at least 20 times more stringent than ribosomal recognition, editing, and other proofreading mechanisms (Reynolds et al, 2010). The fact that crucial genetic code specificities in highly selective interactions with protein enzymes do not involve the ribosomal ribonucleoprotein biosynthetic machinery challenges the “replicators first” origin of life scenario of an ancient RNA world (Caetano-Anollés and Seufferheld, 2013). It also highlights the central functional, mechanistic, and evolutionary roles of tRNA and its recognition determinants, which enable coevolution between nucleic acids and proteins.…”