The central dogma of molecular biology and genetics is pretty straightforward. You take DNA, then you transcribe the desired gene into RNA (usually mRNA) and, once outside of the nucleus, you translate that RNA using ribosomes into amino acids that then form proteins. Those proteins then do the actual function that their original genetic encoding directs. This process is usually rigid and cannot be reversed.

DNA to RNA to proteins, simple as that.

Except when it’s not.

The Exceptions

There have always been a few exceptions and they’re often terrifying. Like how retroviruses utilize a reverse transcription process to insert their own RNA into the genome of their host to make their host cell produce more of the invading virus. It is processes like these that make them so insidious to fight against.

But there’s another exception. It is a more innocuous and rare one, but also a more confusing one. While the central dogma is a good basis for the overall system, there are a lot of other mechanisms at play, especially after the point of transcription into RNA.

It is possible for this RNA to be edited after the fact and change the resulting protein sequence. The main method of this RNA editing happens when the “A” nucleotides (adenosines making up adenine) are modified by ADAR enzymes, which stands for “adenosine deaminases acting on RNA”, into another form called inosine.

During translation to make amino acids, inosine can be recognized instead as a “G” nucleotide (guanosines making up guanine), though it can also bind to other bases, making it extremely versatile. This change effectively alters the original genetic code without actually changing the genome that it was originally transcribed from.

Some Cephalopods Buck The Trend

This change is incredibly rare. Only 3% of human RNA messages have even a single base altered like this. And this number itself is only so high because, out of the 25 sites in total in the human genome that allow this reconfiguration, they are largely conserved genes, meaning they are highly coded for. All in all, such a change is not actually highly conserved and has disappeared from the rest of the human genome because of this.

Researchers from MIT and Israel have recently published a study describing several species in the class Cephalopoda that wildly outstrip this pathetic chance, but only those species. In fact, octopodes, squids, and cuttlefish appear to have a vast majority of their RNA messages changed like this. For practically every RNA message, at least one altered nucleotide event like this occurs, changing the resulting coded for message.

As an example with squids, out of their 20,000 total genes, over 11,000 of them when transcribed lead to an RNA editing event. They also appear to be highly conserved and not allowed to be removed from the genome by natural repair and mutation mechanisms.

What is the end result of this mechanism? The formation of proteins that are not actually coded for within the genome itself, but are nonetheless properly utilized and created by the organism when needed. Which means that there is a whole other layer of genetic instructions hidden away in these particular species that can’t be seen just from a full genetic sequencing.

The Downsides

But there is a trade-off and downside to be had. While this enables species like squids to be highly adaptable to their environment, such as being able to alter certain temperature coding genes at the RNA level when necessary, it also makes them very rigid.

This is because the genes with these sites that invite RNA alteration cannot allow mutations to occur in the genes. Due to the complex RNA structures needed when coding for these sorts of genes, even a single mutation in them can stop the entire gene and resulting RNA from functioning. This, in turn, would likely kill the organism, though it depends on the gene in question. So the genes must be conserved and extensively so.

This means that their adaptability is entirely inherent, already existing in their genomes. But they cannot adapt beyond that. They cannot allow the rampant mutations that other species, including us, use to evolve and fit our changing environments on the fly. If octopodes, squids, or cuttlefish come up against something that their changing RNA structure isn’t fit to handle, they can’t adapt to it by changing their genome.

Will It Work Out?

Such a consequence results in them being very slow to evolve over time. Sure, their ability to apply so many kinds of RNA edits is likely one of the benefits that gives them their intelligence and so many of their flexible capabilities. But it also means that issues like climate change and ocean acidification may be topics they won’t be able to deal with, leading to a widespread die-off of the species as a whole.

Though, on the other hand, maybe not. Perhaps their RNA editing abilities are robust enough even to handle those concerns. They certainly appear to be some of the closest organisms to humans when it comes to mental and developmental complexity. Only time will tell in that regard.

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Study Link

Photo CCs: Expl0717 – Flickr – NOAA Photo Library from Wikimedia Commons

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