The origin of life: RNA and protein co‐evolution on the ancient Earth

Abstract

How life emerged from simple non-life chemicals on the ancient Earth is one of the greatest mysteries in biology. The gene expression system of extant life is based on the interdependence between multiple molecular species (DNA, RNA, and proteins).While DNA is mainly used as genetic material and proteins as functional molecules in modern biology, RNA serves as both genetic material and enzymes (ribozymes). Thus, the evolution of life may have begun with the birth of a ribozyme that replicated itself (the RNA world hypothesis), and proteins and DNA joined later. However, the complete self-replication of ribozymes from monomeric substrates has not yet been demonstrated experimentally, due to their limited activity and stability. In contrast, peptides are more chemically stable and are considered to have existed on the ancient Earth, leading to the hypothesis of RNA-peptide co-evolution from the very beginning. Our group and collaborators recently demonstrated that (1) peptides with both hydrophobic and cationic moieties (e.g., KKVVVVVV) form β-amyloid aggregates that adsorb RNA and enhance RNA synthesis by an artificial RNA polymerase ribozyme and (2) a simple peptide with only seven amino acid types (especially rich in valine and lysine) can fold into the ancient β-barrel conserved in various enzymes, including the core of cellular RNA polymerases. These findings, together with recent reports from other groups, suggest that simple prebiotic peptides could have supported the ancient RNA-based replication system, gradually folded into RNA-binding proteins, and eventually evolved into complex proteins like RNA polymerase.ancient proteins, central dogma, origin of life, peptide, RNA world | INTRODUCTIONAt the core of the present life system, RNA and protein mutually synthesize each other: ribosomes (RNA) synthesize proteins, and RNA polymerases (protein) synthesize RNA. This suggests that our complex genetic system or the central dogma resulted from a long co-evolutionary process between RNAs and proteins (Lanier et al., 2017). It is widely accepted that RNA preceded protein (the RNA world hypothesis), as it can simultaneously store genetic information and perform catalytic functions, while modern proteins must be encoded by nucleic acids (Gilbert, 1986;Joyce, 1989).To prove this RNA-first scenario, an artificial ribozyme with an RNA-dependent RNA polymerase activity (RNA polymerase ribozyme [RPR]) has been developed as a model for the ancient self-replicating RNA molecule in the RNA world (Figure 1a) (Johnston et al., 2001;Wochner et al., 2011). However, the activity of RPR is still not sufficient to accomplish self-replication from monomeric substrates (NTPs), although its partial self-synthesis has been reported in recent years (Attwater et al., 2018;Tjhung et al., 2020). One likely reason for This article is part of the special issue "Emergence in Biological Systems: Challenges to Bridging Hierarchies."

Why is Abiogenesis Such a Tough Nut to Crack?

“…In 2023, Tagami and Li [93] found that peptides with both hydrophobic and cationic moieties (e.g., KKVVVVVV) form beta-amyloid aggregates that adsorb RNA and enhance RNA synthesis by an artificial RNA polymerase ribozyme. In addition, they found that a simple peptide with only seven amino acid types (especially rich in valine and lysine) can fold into the ancient beta-barrel conserved in various enzymes, including the core of cellular RNA polymerases.…”

Why we are made of proteins and nucleic acids: Structural biology views on extraterrestrial life

“…Peptides with secondary structures might have been intermediates between randomly synthesized prebiotic peptides and folded proteins [1][2][3]. For example, in 1975, Brack and Orgel reported that a simple peptide with alternating valine and lysine residues can self-assemble into large β-sheet structures [4].…”

“…Peptide assemblies with secondary structures might also have played essential roles in co-evolution with RNA [1][2][3]12]. Our group has recently demonstrated that a peptide with hydrophobic and cationic moieties (P43: AKKVWIIMGGS) can form insoluble assemblies containing β-amyloid structures that accumulate RNA on their surfaces [13].…”

“…The formation of hydrophobic cores is essential for protein folding. Although simple β-amyloids or α-helical assemblies can be formed relatively easily [1][2][3][4][5][6], the formation of tertiary structures seems to be much more complicated. For protein stability, it is generally considered important to arrange the hydrophobic side chains without gaps in the hydrophobic cores.…”

Biological Catalysis and Information Storage Have Relied on N-Glycosyl Derivatives of β-D-Ribofuranose since the Origins of Life

“…Recently, this concept has been significantly modified, and new theories present the origin of life as RNA catalysis facilitated by amino acidor peptide-based cofactors or the "RNA-peptide World". Nevertheless, each scenario had to be based on the prebiotic synthesis of activated nucleotides and RNA molecules, including ribozymes [45][46][47][48][49][50][51][52][53][54][55]. Following this remark, the very origin of any RNA-based World(s) from inanimate matter appears particularly interesting.…”