Testing a biosynthetic theory of the genetic code: Fact or artifact?

Ronneberg, Terres A.; Landweber, Laura F.; Freeland, Stephen J.

doi:10.1073/pnas.250403097

Cited by 71 publications

(74 citation statements)

References 41 publications

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“…What amino acids were the primordial ones and how the new amino acids were added to the genetic repertoire are unknown and under debate (4,19,21,34). In addition, if RNA-amino acid interactions influenced the organization of the code, the pervasiveness of these interactions, and the interplay between such interactions and other potential driving forces, are also unknown.…”

Section: Discussionmentioning

confidence: 99%

“…Several methods have been devised to generate random genetic codes for analyzing code properties (18)(19)(20), and different generators have yielded different results in some cases (19,21,22). To determine if our findings were independent of the code-generation methods, we employed all three methods in our correlation analyses.…”

Section: Codons or Anticodons For Select Amino Acids Are Enriched Neamentioning

confidence: 99%

“…The first method (RAND method) maintains the number of codons per amino acid as dictated by the canonical code and randomizes the positions of the amino acids (19) (Methods). The second method (NNY method) is similar to the RAND method but imposes the restriction of not splitting NNY blocks (21). No evidence exists in nonstandard genetic codes that suggest translation can distinguish between codons occupying a NNY block (23), and thus it has been proposed that NNY codons should not be split when generating random codes (21).…”

Section: Codons or Anticodons For Select Amino Acids Are Enriched Neamentioning

confidence: 99%

“…The second method (NNY method) is similar to the RAND method but imposes the restriction of not splitting NNY blocks (21). No evidence exists in nonstandard genetic codes that suggest translation can distinguish between codons occupying a NNY block (23), and thus it has been proposed that NNY codons should not be split when generating random codes (21). The third method (SYN method) maintains the exact block structure of the canonical code and randomizes the amino acid in each block (20).…”

Section: Codons or Anticodons For Select Amino Acids Are Enriched Neamentioning

confidence: 99%

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Imprints of the genetic code in the ribosome

Johnson

Wang

2010

Proc. Natl. Acad. Sci. U.S.A.

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The establishment of the genetic code remains elusive nearly five decades after the code was elucidated. The stereochemical hypothesis postulates that the code developed from interactions between nucleotides and amino acids, yet supporting evidence in a biological context is lacking. We show here that anticodons are selectively enriched near their respective amino acids in the ribosome, and that such enrichment is significantly correlated with the canonical code over random codes. Ribosomal anticodon-amino acid enrichment further reveals that specific codons were reassigned during code evolution, and that the code evolved through a two-stage transition from ancient amino acids without anticodon interaction to newer additions with anticodon interaction. The ribosome thus serves as a molecular fossil, preserving biological evidence that anticodonamino acid interactions shaped the evolution of the genetic code.evolution of the genetic code | stereochemical hypothesis | anticodonamino acid association | codon reassignment | RNA-protein interaction T he origin and evolution of the genetic code is a critical transition in the evolution of all modern organisms (1). Understanding why the genetic code evolved to its modern form is as important, if not more so, as knowing the code itself (2), as it is central to understanding major evolutionary breakthroughs. However, the universality of the code is also its downfall with regard to studying its formation, as no organisms exist containing a primitive or intermediate genetic code for comparison. Although multiple hypotheses have been proposed to explain why codons are selectively assigned to specific amino acids (3, 4), empirical data are extremely rare and difficult to obtain (5-8), leaving many theories in the realm of conjecture. One theory addressing this challenging question is the stereochemical hypothesis, which postulates that the genetic code developed from interactions between anticodon-or codon-containing polynucleotides and their respective amino acids (5, 9). This theory is supported by RNA aptamer experiments, in which RNA molecules evolved to bind specific amino acids in vitro are enriched with anticodon and codon elements for the amino acid (6-8, 10). Codons for arginine have also been found to confer binding specificity for arginine in the self-splicing group I introns (11). Nonetheless, the biological relevance of these aptamers and introns to genetic code evolution is unknown, and no further in vivo data exist to support this hypothesis.If chemical or physical interactions between nucleotides and amino acids did influence the evolution of the genetic code, relics of this evolution may be present in modern cells. In particular, we may uncover such imprints within RNA-binding proteins and RNAprotein interactions. The ribosome presents an excellent model for the study of these potential interactions, as it is a large ribonucleoprotein complex with some 50 proteins interacting extensively with the ribosomal RNAs (rRNAs) for stability and structure (Fig. 1A) (...

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Section: Discussionmentioning

confidence: 99%

Section: Codons or Anticodons For Select Amino Acids Are Enriched Neamentioning

confidence: 99%

Section: Codons or Anticodons For Select Amino Acids Are Enriched Neamentioning

confidence: 99%

Section: Codons or Anticodons For Select Amino Acids Are Enriched Neamentioning

confidence: 99%

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Imprints of the genetic code in the ribosome

Johnson

Wang

2010

Proc. Natl. Acad. Sci. U.S.A.

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“…The presented computer modeling and the theory on which it is based should be helpful in understanding the evolution of today's genetic code (22,23). The theory should also be useful in the search for ways to create novel devices by self-organization (24)(25)(26).…”

Section: Library Of Devices Ck Of Kind Kmentioning

confidence: 99%

Computer-modeling origin of a simple genetic apparatus

Kühn¹

2001

Proc. Natl. Acad. Sci. U.S.A.

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This computer simulation is based on a model of the origin of life proposed by H. Kuhn and J. Waser, where the evolution of short molecular strands is assumed to take place in a distinct spatiotemporal structured environment. In their model, the prebiotic situation is strongly simplified to grasp essential features of the evolution of the genetic apparatus without attempts to trace the historic path. With the tool of computer implementation confining to principle aspects and focused on critical features of the model, a deeper understanding of the model's premises is achieved. Each generation consists of three steps: (i) construction of devices (entities exposed to selection) presently available; (ii) selection; and (iii) multiplication of the isolated strands (R oligomers) by complementary copying with occasional variation by copying mismatch. In the beginning, the devices are single strands with random sequences; later, increasingly complex aggregates of strands form devices such as a hairpin-assembler device which develop in favorable cases. A monomers interlink by binding to the hairpin-assembler device, and a translation machinery, called the hairpin-assembler-enzyme device, emerges, which translates the sequence of R1 and R2 monomers in the assembler strand to the sequence of A1 and A2 monomers in the A oligomer, working as an enzyme.

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“Terrestrial” Amino Acids and their Evolution

Freeland

2009

Amino Acids, Peptides and Proteins in Organic Chemistry

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Testing a biosynthetic theory of the genetic code: Fact or artifact?

Cited by 71 publications

References 41 publications

Imprints of the genetic code in the ribosome

Imprints of the genetic code in the ribosome

Computer-modeling origin of a simple genetic apparatus

“Terrestrial” Amino Acids and their Evolution

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