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The Hypothesis that the Genetic Code Originated in Coupled Synthesis of Proteins and the Evolutionary Predecessors of Nucleic Acids in Primitive Cells.

Francis BR - Life (Basel) (2015)

Bottom Line: A primitive cell capable of supporting electron transport, thioester synthesis, reduction reactions, and synthesis of polyesters and polypeptides is proposed.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular Biology, University of Wyoming, Laramie, WY 82071, USA. brianrf@uwyo.edu.

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.

No MeSH data available.


β-Polyester synthesis. (A) Enzyme catalyzed synthesis of poly(β-l-hydroxybutyric acid). The CH3 side chains in poly(β-l-hydroxybutyric acid) occur at repeating distances along the polyester chain and point in the same direction relative to the backbone; (B,C) Proposed non-enzymatic synthesis of poly(β-d-malic acid) (B) and poly(β-d-malamide) (C) in primitive cells. The double hydrogen bonds of the side chains occur at repeating distances and are in the same direction relative to the backbone. Arrows indicate directions of possible hydrogen bonds. * indicates chiral carbon atom.
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life-05-00467-f003: β-Polyester synthesis. (A) Enzyme catalyzed synthesis of poly(β-l-hydroxybutyric acid). The CH3 side chains in poly(β-l-hydroxybutyric acid) occur at repeating distances along the polyester chain and point in the same direction relative to the backbone; (B,C) Proposed non-enzymatic synthesis of poly(β-d-malic acid) (B) and poly(β-d-malamide) (C) in primitive cells. The double hydrogen bonds of the side chains occur at repeating distances and are in the same direction relative to the backbone. Arrows indicate directions of possible hydrogen bonds. * indicates chiral carbon atom.

Mentions: Hydrogen bonding between the purines and pyrimidines of nucleic acids is the foundation of genetics. How did genetics start if purines and pyrimidines were not available from the environment or from synthesis inside early cells? Consideration must be given to the possibility that genetic polymers started with aliphatic side chains rather than purines and pyrimidines. Returning to the structure of PHBA, which is a simple linear β-polyester formed from β-l-hydroxbutyryl-CoA monomers, it is interesting that the methyl groups occur at repeating positions along the polyester chain and the homochiral nature of the polymer ensures that the methyl side chains all point in the same direction relative to the polyester backbone (Figure 3A).


The Hypothesis that the Genetic Code Originated in Coupled Synthesis of Proteins and the Evolutionary Predecessors of Nucleic Acids in Primitive Cells.

Francis BR - Life (Basel) (2015)

β-Polyester synthesis. (A) Enzyme catalyzed synthesis of poly(β-l-hydroxybutyric acid). The CH3 side chains in poly(β-l-hydroxybutyric acid) occur at repeating distances along the polyester chain and point in the same direction relative to the backbone; (B,C) Proposed non-enzymatic synthesis of poly(β-d-malic acid) (B) and poly(β-d-malamide) (C) in primitive cells. The double hydrogen bonds of the side chains occur at repeating distances and are in the same direction relative to the backbone. Arrows indicate directions of possible hydrogen bonds. * indicates chiral carbon atom.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4390864&req=5

life-05-00467-f003: β-Polyester synthesis. (A) Enzyme catalyzed synthesis of poly(β-l-hydroxybutyric acid). The CH3 side chains in poly(β-l-hydroxybutyric acid) occur at repeating distances along the polyester chain and point in the same direction relative to the backbone; (B,C) Proposed non-enzymatic synthesis of poly(β-d-malic acid) (B) and poly(β-d-malamide) (C) in primitive cells. The double hydrogen bonds of the side chains occur at repeating distances and are in the same direction relative to the backbone. Arrows indicate directions of possible hydrogen bonds. * indicates chiral carbon atom.
Mentions: Hydrogen bonding between the purines and pyrimidines of nucleic acids is the foundation of genetics. How did genetics start if purines and pyrimidines were not available from the environment or from synthesis inside early cells? Consideration must be given to the possibility that genetic polymers started with aliphatic side chains rather than purines and pyrimidines. Returning to the structure of PHBA, which is a simple linear β-polyester formed from β-l-hydroxbutyryl-CoA monomers, it is interesting that the methyl groups occur at repeating positions along the polyester chain and the homochiral nature of the polymer ensures that the methyl side chains all point in the same direction relative to the polyester backbone (Figure 3A).

Bottom Line: A primitive cell capable of supporting electron transport, thioester synthesis, reduction reactions, and synthesis of polyesters and polypeptides is proposed.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular Biology, University of Wyoming, Laramie, WY 82071, USA. brianrf@uwyo.edu.

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.

No MeSH data available.