Augmented genetic decoding: global, local and temporal alterations of decoding processes and codon meaning

Journal name:
Nature Reviews Genetics
Year published:
Published online


The non-universality of the genetic code is now widely appreciated. Codes differ between organisms, and certain genes are known to alter the decoding rules in a site-specific manner. Recently discovered examples of decoding plasticity are particularly spectacular. These examples include organisms and organelles with disruptions of triplet continuity during the translation of many genes, viruses that alter the entire genetic code of their hosts and organisms that adjust their genetic code in response to changing environments. In this Review, we outline various modes of alternative genetic decoding and expand existing terminology to accommodate recently discovered manifestations of this seemingly sophisticated phenomenon.

At a glance


  1. Freezing and melting of genetic decoding.
    Figure 1: Freezing and melting of genetic decoding.

    a | The standard genetic code. b | A timeline illustrating major events that shaped our current understanding of genetic decoding. Early discoveries that led to the formation of the universal principles of genetic decoding are shown in blue. More recent findings that have revealed evolvability and the flexibility of genetic decoding are shown in red.

  2. Components that shape alternative genetic decoding.
    Figure 2: Components that shape alternative genetic decoding.

    The figure illustrates a distinction between codon reassignment and recoding, which are sometimes confused in the literature. Collective representation (assembled from several examples from different organisms) of stop codon reassignment (part a) and recoding (part b) is shown. Different ways by which codon meaning can be reassigned, as exemplified by the AGA codon (part a), are shown. This codon is known to have four different meanings depending on the variant genetic code used in the corresponding organism. Codon reassignment can originate as a result of changes in tRNAs, aminoacyl-tRNA synthetases (aaRSs) or release factors (RFs), although it may also involve other components, as exemplified by AGA reassignment to stop codon in vertebrate mitochondria. Codon reassignment affects the expression of all genes in the organism that use the reassigned codon. Two recoding events are shown (part b). Codon redefinition (left) is exemplified with a schematic of selenocysteine (Sec; single letter code U) insertion at UGA codons in eukaryotes, which requires a Sec insertion sequence (SECIS) element in the 3′ UTR, a specialized tRNA, an elongation factor eEFSec and auxiliary protein SECIS-binding protein 2 (SBP2). Ribosomal frameshifting (right) is shown as a collective representation of several frameshifting events. Shine–Dalgarno interactions with ribosomal RNA stimulate frameshifting in bacterial release factor 2 mRNA decoding. A stimulatory downstream RNA pseudoknot structure is present in many eukaryotic antizyme mRNAs. Frameshifting in antizymes is also known to be sensitive to polyamine concentration. These examples illustrate how (in contrast to codon reassignment), recoding events are dependent on favourable sequence contexts that locally alter the interpretation of the codon sequences.

  3. Relationship between nucleotide sequences and alternatively decoded proteins.
    Figure 3: Relationship between nucleotide sequences and alternatively decoded proteins.

    Nucleotide sequences are depicted as three horizontal boxes representing three different reading frames. Start (green) and stop (red) codons are shown as vertical lines. The sequences that are translated into proteins are shown as horizontal bars with amino- and carboxy-terminal ends indicated. The purple bars correspond to standard decoding and orange bars correspond to alternative events. Transitions between reading frames are denoted with broken lines. tmRNA, transfer and messenger RNA.


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  1. School of Biochemistry and Cell Biology, University College Cork, Ireland.

    • Pavel V. Baranov,
    • John F. Atkins &
    • Martina M. Yordanova
  2. Department of Human Genetics, University of Utah, 15 N 2030 E Rm. 7410, Salt Lake City, Utah 84112–5330, USA.

    • John F. Atkins

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  • Pavel V. Baranov

    Pavel V. Baranov's research is focused on the mechanisms of mRNA translation, in particular using high-throughput biochemical methods and phylogenetic approaches. He is a principal investigator at University College Cork, Ireland. Pavel completed his Ph.D. at Moscow State University, Russia, while studying the structure of the bacterial ribosome and worked as a postdoctoral researcher in the Max Planck Institute for Molecular Genetics in Berlin, Germany, and later in the Department of Human Genetics at the University of Utah, Salt Lake City, USA. Pavel V. Baranov's laboratory homepage.

  • John F. Atkins

    John F. Atkins is a molecular geneticist whose initial studies on frameshift mutant suppression and leaking led him to start studying recoding in the 1980s. He is also interested in 'The RNA World' hypothesis. John F. Atkins is a research professor at University College Cork, Ireland, and in the Department of Human Genetics, University of Utah, Salt Lake City, USA.

  • Martina M. Yordanova

    Martina M. Yordanova is a graduate student in the laboratory of John F. Atkins at University College Cork, Ireland. She is completing the last year of her Ph.D., which focuses on the mechanism of polyamine sensing by ribosomal frameshifting in antizyme mRNAs.

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