“The very strangeness of Echinodermata is partly responsible for the dedication that specialists in the group feel. We revel in their weirdness.”
Given that every biology student in the world has been introduced to the standard genetic code, and likely uses it frequently, it is kind of baffling that so few of us ever bother to think much about it. As a longtime lover of systematics/molecular evolution, the knowledge that the “universal genetic code” is not actually universal has always caused me some level of concern when imagining how scientists cope with such an issue or if they even cope with the issue at all.
Usually when you look this up you find a lot of “the code is essentially universal, only a few exceptions have been found” which would imply that maybe one or two extremely obscure microorganisms violated this rule slightly. But mammals mitochondria actually contains four out of 64 codons that do not match the universal code. Echinoderms, yeast, platyhelminth worms, all follow slightly different mitochondrial DNA codes and protozoan and some bacteria even follow different nuclear DNA codes (nuclear being the only DNA bacteria have).
While there are 64 codons, there are fewer than 64 tRNAs, which use an anticodon sequence to recognize a codon on mRNA and carry the appropriate amino acid at the other end. Different tRNAs with the various amino acids will sort of float in and out until the right one’s bound. The third position of the anticodon (the ‘wobble position’) however, binds very loosely to the DNA which is why the tRNA usually relies on recognizing the first two nucleotides. Some amino acids can have multiple tRNAs recognizing them but RNA modifications in the anticodon region of tRNAs can result in the evolution of a deviation to the universal genetic code. The echinoderm’s genetic code evolution is particularly intriguing which is hardly surprising given everything else about them.
A recent Nature paper shows an example of how this works in echinoderms. In echinoderm mitochondrial DNA, the codon AAA, which according to the “universal code” should code for a lysine, actually codes for an asparagine. Analyzing the tRNALys isolated from a sea urchin, they discovered a modified hydroxylated nucleoside; hydroxyl-N6-threonylcarbamoyladenosine. This modified nucleoside adjacent to the anticodon prevents the mt-tRNALys from misreading AAA as lysine, allowing AAA to code for an asparagine.
Mitochondria generally use a codon-anticodon pairing rule that allows unmodified uridine at the anticodon first position to pair with all four nucleotides at the third codon position. When an amino acid only has two codons corresponding to it, the G forms a base-pair with pyrimidine, and modified uridines (5-carboxymethylaminomethyl-uridine being a commonly heard modification to the wobble position base) can discriminate purines from pyrimidines. The presence of a pseudouridine in starfish mt-tRNAAsn in the middle of the anticodon allows the tRNA to decode the AAA codon more efficiently than the unmodified tRNA. Also interesting, the mt-tRNAs possessing anticodons similar to tRNAAsn, but which only decode two codons each (tRNAHis, tRNAAsp and tRNATyr) all possess unmodified U (position 35), further indicating pseudouridine (Ψ35) is important for decoding the three codons.
While certainly not all examples of a modified genetic code work quite this way, it’s intriguing to realize how something generally portrayed as being set in stone, is relatively labile and dynamic.
Given that systematics has favored mitochondrial DNA for many phylogenetic analyses, this could have an effect on the results if using an amino acid alignment or a distance matrix where each amino acid change is weighted a certain amount. You could imagine an alignment between mammals, echinoderms, and reptiles for example, where an AAA to an AAG would be a synonymous mutation (as in, not changing the protein) in mammals and reptiles, but a nonsynonymous mutation (changing the amino acid) in echinoderms, thus deserving a different score. AGA and AGG which both code Arginine in the ‘universal’ code, code for a stop codon in our mtDNA, while our nuclear DNA’s stop codon (UGA), codes a tryptophan. An AUA isoleucine in our nuclear DNA is read as a methionine in our mtDNA. There are likely many more “exceptions to the rule” that we have no idea exist.
- Hydroxylation of a conserved tRNA modification establishes non-universal genetic code in echinoderm mitochondria. Asuteka Nagao, Mitsuhiro Ohara, Kenjyo Miyauchi, Shin-ichi Yokobori, Akihiko Yamagishi, Kimitsuna Watanabe & Tsutomu Suzuki. Nature Structural & Molecular Biology (2017).
The presence of pseudouridine in the anticodon alters the genetic code: a possible mechanism for assignment of the AAA lysine codon as asparagine in echinoderm mitochondria. Nucleic Acids Res.27, 1683–1689 (1999)., &