Abstract

Although analysis of the genetic code has allowed explanations for its evolution to be proposed, little evidence exists in biochemistry and molecular biology to offer an explanation for the origin of the genetic code. In particular, two features of biology make the origin of the genetic code difficult to understand. First, nucleic acids are highly complicated polymers requiring numerous enzymes for biosynthesis. Secondly, proteins have a simple backbone with a set of 20 different amino acid side chains synthesized by a highly complicated ribosomal process in which mRNA sequences are read in triplets. Apparently, both nucleic acid and protein syntheses have extensive evolutionary histories. Supporting these processes is a complex metabolism and at the hub of metabolism are the carboxylic acid cycles. This paper advances the hypothesis that the earliest predecessor of the nucleic acids was a β-linked polyester made from malic acid, a highly conserved metabolite in the carboxylic acid cycles. In the β-linked polyester, the side chains are carboxylic acid groups capable of forming interstrand double hydrogen bonds. Evolution of the nucleic acids involved changes to the backbone and side chain of poly(β-d-malic acid). Conversion of the side chain carboxylic acid into a carboxamide or a longer side chain bearing a carboxamide group, allowed information polymers to form amide pairs between polyester chains. Aminoacylation of the hydroxyl groups of malic acid and its derivatives with simple amino acids such as glycine and alanine allowed coupling of polyester synthesis and protein synthesis. Use of polypeptides containing glycine and l-alanine for activation of two different monomers with either glycine or l-alanine allowed simple coded autocatalytic synthesis of polyesters and polypeptides and established the first genetic code. A primitive cell capable of supporting electron transport, thioester synthesis, reduction reactions, and synthesis of polyesters and polypeptides is proposed. The cell consists of an iron-sulfide particle enclosed by tholin, a heterogeneous organic material that is produced by Miller-Urey type experiments that simulate conditions on the early Earth. As the synthesis of nucleic acids evolved from β-linked polyesters, the singlet coding system for replication evolved into a four nucleotide/four amino acid process (AMP = aspartic acid, GMP = glycine, UMP = valine, CMP = alanine) and then into the triplet ribosomal process that permitted multiple copies of protein to be synthesized independent of replication. This hypothesis reconciles the “genetics first” and “metabolism first” approaches to the origin of life and explains why there are four bases in the genetic alphabet.

Highlights

  • Despite considerable research devoted to studying how life started on Earth, no widely accepted theory of the origin of life has emerged

  • I proposed that ribosomal protein synthesis evolved from coupled synthesis of nucleic acids and proteins

  • If tholin formed primitive electron-transporting cell membranes, what was the electron acceptor and how was the energy from electron transport harnessed for synthesis within the cells? Because thioesters played a central role in primitive cell synthesis, the question becomes: How was electron transport linked to thioester synthesis? Before enzymes were available, this would probably have required an alternate type of catalyst

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Summary

Introduction

Despite considerable research devoted to studying how life started on Earth, no widely accepted theory of the origin of life has emerged. Such a theory would have to explain how an initial simple system was established and how the simple system evolved into the complex biological system. I proposed that ribosomal protein synthesis evolved from coupled synthesis of nucleic acids and proteins. I extended this hypothesis to describe how the coupled process evolved with continuity into ribosomal protein synthesis and, in so doing, provided an alternative to the RNA world hypothesis [5]. I present the argument for coupled protein and nucleic acid synthesis in an updated and different way from that which was published in 2000

Autocatalysis in the Origin of Life
Thioesters Were Used for Synthesis in Primitive Cells
Thioester Bonds Were Used to Form Ester and Amide Bonds
Energy Transduction in Biology
Formation of the Earliest Cell Membranes
Iron Sulfide in Origin of Life Scenarios
10. FeS Cluster Biochemistry and Chemistry
11. Biochemical Reduction of Disulfides and Thioester Formation
12. A Proposal for Primitive Cellular Synthesis of Thioesters
14. Reduction and Carboxylation Reactions inside Primitive Cells
15. Polypeptide synthesis
15. Base Catalysis in Early Metabolism
16. A Model for the Simple System within a Primitive Cell
17. Genetic Polymers Were Initially Produced from Aliphatic Monomers
19. Coenzyme A as a Relic of Early Nucleic Acid Evolution
20. Coupling of β-Polyester Synthesis and Protein Synthesis
21. A Thiol at the N-Terminal End of Early Proteins
22. Autocatalysis Revisited
23. Replication of β-Polyesters
24. Evolution of the Singlet Coding System into the Triplet Coding System
26.1. An Evolutionary Pathway from Primitive Cells to Biology
26.2. Comparisons with Other Proposals on the Origins of Cells
26.3. Why Is the Simple Method of Thioester Synthesis Not Used in Biology?
26.6. Reversible Reactions in Primitive Cells
26.8. Did “Chemical Evolution” Happen before Biological Evolution?
Full Text
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