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Rewiring the keyboard: evolvability of the genetic code

Key Points

  • There are many variations in the genetic code, both in nuclear and mitochondrial genomes, but all are relatively recent modifications of the 'canonical' code found in the last common ancestor.

  • The recent evolution of the genetic code relies on changes in components of the translation apparatus. In particular, many changes are due to base modifications that occur after transcription.

  • Three theories have attempted to explain the range of changes to the genetic code:

    1. Codon capture: biased mutations can eliminate certain codons from the genome, which are reassigned by neutral processes (that is, in the absence of selection).

    2. Genome minimization: the code evolves to minimize the number of tRNAs required for translation.

    3. Codon ambiguity: evolution of the genetic code is adaptive and occurs through an intermediate stage in which a codon can be translated into more than one amino acid.

  • We find statistical support for the last two of these theories.

  • Changes in the genetic code that are revealed by future studies will be used to test the specific predictions of each of these theories. Future work will also further clarify the roles of mutation and selection in producing new genetic codes.

Abstract

The genetic code evolved in two distinct phases. First, the 'canonical' code emerged before the last universal ancestor; subsequently, this code diverged in numerous nuclear and organelle lineages. Here, we examine the distribution and causes of these secondary deviations from the canonical genetic code. The majority of non-standard codes arise from alterations in the tRNA, with most occurring by post-transcriptional modifications, such as base modification or RNA editing, rather than by substitutions within tRNA anticodons.

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Figure 1: Overview of translation.
Figure 2: Composite phylogeny of variant codes.
Figure 3: The genetic code and its variants.

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Acknowledgements

S.J.F. is supported by a Human Frontier Science Program fellowship.

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FURTHER INFORMATION

The Tree of Life

The RNA world web site

Laura Landweber's lab page

RNA editing

ENCYCLOPEDIA OF LIFE SCIENCES

Transfer RNA

RNA editing

Genetic code and its variants

tRNA modification

Glossary

DIPLOMONADS

Among the earliest-diverging eukaryotes, these unicellular organisms have two nuclei, but lack mitochondria. The gastrointestinal parasite Giardia is a diplomonad.

RELEASE FACTORS

Proteins involved in translation termination that specifically recognize stop codons and catalyse the disassembly of the translation complex.

AMINOACYL-tRNA SYNTHETASE

The enzyme that attaches an amino acid to its cognate tRNA(s).

WOBBLE RULES

An extension to Watson–Crick base pairing, these rules indicate that, in the context of the first anticodon position of the tRNA (complementary to the third codon position), more flexibility allows non-standard base pairs (such as G with U rather than with C).

RIBOZYME

RNA that can perform a catalytic task, such as the self-splicing Group I intron in the ciliate Tetrahymena.

THIOL

A thiol (or sulphydryl) group is a chemical group that contains sulphur and hydrogen.

SUPPRESSOR MUTATION

A mutation that counteracts the effects of another mutation. A suppressor mutation maps at a different site to that of the mutation that it counteracts, either within the gene or at a more distant locus. Mutations in tRNAs often act as suppressors, because they can change the meaning of the mutated codon back to the original (albeit usually at a low level, because efficient suppressors are often lethal).

RNA EDITING

Changes in the RNA sequence after transcription is completed. Examples include modification of C to U or of A to I by deamination, or insertion and/or deletion of particular bases.

FAMILY BOX

A set of four codons that are identical at the first two positions, differ only at the third position and code for the same amino acid. For instance, GUU, GUC, GUA and GUG comprise a family box for valine in all known codes.

BINOMIAL TEST

If an observation has only two possible outcomes and there are multiple observations, the binomial distribution gives the probability that x or more outcomes of a given type would occur by chance.

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Knight, R., Freeland, S. & Landweber, L. Rewiring the keyboard: evolvability of the genetic code. Nat Rev Genet 2, 49–58 (2001). https://doi.org/10.1038/35047500

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