Imprints of the genetic code in the ribosome

Abstract

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) (...

Genetic Hotels for the Standard Genetic Code: Evolutionary Analysis Based upon Novel Three-Dimensional Algebraic Models

“…Johnson and Wang (2010), looking for relics of the underlying force driving the evolution of the genetic code, found that it is the anticodonamino acid association, but not the codon-amino acid association that correlates with the genetic code. This conclusion advances the stereochemical hypothesis by pinpointing anticodon-amino acid interaction as the potential drive for code formation.…”

“…Not only the tRNA or the aaRS have been implicated in the evolution of the SGC but also the ribosome seems to have imprints from an early evolution stage of life to establish the translation of the genetic code before LUCA (Fox and Naik 2004;Johnson and Wang 2010). Johnson and Wang (2010), looking for relics of the underlying force driving the evolution of the genetic code, found that it is the anticodonamino acid association, but not the codon-amino acid association that correlates with the genetic code.…”

“…The original stereochemical hypothesis proposes that the genetic code is shaped by interactions between amino acids and cognate coding triplets, which can be codons or anticodons. Johnson and Wang (2010) proposed that the SGC evolved through a two-stage transition. Their finding on ribosomal anticodon-amino acid enrichment, when compared with the consensus chronology of amino acids built on 60 criteria (Trifonov 2000), revealed a distinct stage for the evolution of the canonical code.…”

Altered Tryptophan Metabolism as a Paradigm for Good and Bad Aspects of Immune Privilege in Chronic Inflammatory Diseases

“…Though murine CD8 − and CD8 + DC subsets expressed IDO protein in response to IFNγ treatment, only CD8 + DCs produced kynurenine, indicating IDO enzyme activity (Fallarino et al, 2002). Systemic treatments with soluble CTLA4 (CTLA4-Ig) and relatively high doses of TLR9 ligands (CpGs) were also able to induce CD8 + DCs to express functional IDO by ligating B7 or TLR9 molecules and inducing IDO via IFNα signaling in a rare, but distinctive subset of splenic CD19 + DCs co-expressing CD8, the plasmacytoid DC (pDC) marker B220, as well as CD19 and other B cell markers (Grohmann et al, 2002; Mellor et al, 2003, 2005;Baban et al, 2005;Johnson et al, 2010). In humans, monocyte-derived DCs competent to express IDO in response to IFNγ were a discrete subset of DCs expressing the chemokine receptor CCR6 and the pDC marker CD123 (Munn et al, 2002), and human DCs expressing IDO in response to CpGs also exhibited pDC attributes (Chen et al, 2008).…”

“…For this reason pDCs may be critical mediators of hyper-immune syndromes since they are major (but not exclusive) sources of type I IFNs, especially in response to pathogen-associated molecular patterns (PAMPs) such as TLRs. It may be pertinent that IDO-competent DCs in humans and mice exhibit attributes that overlap with those of conventional pDCs, as well as other lymphoid and myeloid subsets (Munn et al, 2002; Chen et al, 2008;Johnson et al, 2010). Nevertheless, the role of IFNs, and the cells that produce IFNs, in hyper-immune syndromes is far from clear as IFNs mediate multiple downstream effects that encompass immune stimulatory and immune regulatory pathways.…”