Computational study suggests alternative coding in mitochondrial genomes may be more common than previously believed
By Melissa Lee Phillips | April 25, 2006
The mitochondrial genetic code in some arthropods contains an RNA-to-protein translation never seen before, according to a new study in Public Library of Science (PLoS) Biology. Using an automated genomics-based method, the authors found that translation of the RNA triplet AGG has changed many times in the evolutionary history of arthropods -- hinting that alternative genetic codes in mitochondrial genomes may be more common than suspected, the authors say.
"I think we're really looking here at the beginnings of a landslide change to recognizing the code is far more malleable than early dogma would have us believe," said Stephen Freeland of the University of Maryland, Baltimore County, who was not involved in the study.
Scientists have reported unusual amino acid translations in nuclear genomes of yeasts and ciliates, as well as in mitochondrial genomes of several metazoans. These coding variants were usually discovered by comparative sequence analysis: If one species consistently uses a different RNA codon than other species in well-conserved protein regions, researchers reasoned that the odd codon's translation has changed.
To search for mitochondrial genetic codes that might have been missed in previous studies, Federico Abascal of the University of Vigo and the National Museum of Natural Sciences in Spain and his colleagues automated comparative sequence analysis, and used it to analyze the mitochondrial codes of 626 metazoan species.
Their analysis predicted that several groups of arthropods translate the triplet AGG as lysine -- even though it corresponds to arginine in the canonical genetic code, and to serine in almost all other invertebrate mitochondria. When the authors then compared AGG translation preference with arthropod phylogenies, they found that this coding has likely changed multiple times within different groups of arthropods.
According to the authors' ancestral reconstruction, AGG was reassigned from serine to lysine at the origin of the arthropod phylum. Some arthropod lineages later reverted back to serine translation. By analyzing how various subgroups of arthropods likely translate AGG, the researchers found evidence that some lineages have switched back and forth between the two amino acids multiple times in their histories. "The pattern of parallel reassignments is surprising," Abascal told The Scientist in an Email. "Reassignments occur even within an insect order, [which] suggests that the AGG codon is highly unstable."
He and his co-workers also found that changes in AGG's meaning corresponded to changes in tRNA anticodon sequences for both lysine and serine, suggesting that vacillating point mutations in these anticodons may have caused repeated changes in AGG's translation, Abascal said.
The pairing between AGG and the lysine tRNA anticodon also suggests another novelty: a non-standard pairing between G and U in the middle triplet position. Such "wobble" pairings are common at the third codon position, but "in the entire history of the study of coding, this would be the first second-position wobble," said Michael Yarus of the University of Colorado at Boulder, who was not involved in the study. "I think that's the most uncertain part of the whole story." According to Abascal, it's possible that the middle tRNA base undergoes post-transcriptional modification that allows it to bind more effectively to AGG.
"Using a lot of genomic data to study this question... yields a more convincing conclusion than doing this analysis in a less-automated way," said Yarus. "A lot of interesting biology is hidden within the vastness of the sequence databases." Indeed, Abascal added that he and his colleagues are planning to extend the analyses to other organisms. "Other phyla not well sampled yet could give us other surprises."
Melissa Lee Phillips
Links within this article
D. Secko, "Extending the genetic code," The Scientist, August 15, 2003.
F. Abascal et al., "Parallel evolution of the genetic code in arthropod mitochondrial genomes," Public Library of Science Biology, May 2006.
S. Blackman, "Discovering the 21st Amino Acid ... Again?," The Scientist, October 11, 2004.
R.D. Knight et al., "Rewiring the keyboard: Evolvability of the genetic code," Nature Reviews Genetics, January 2001.