by Janice Nigro
Scientists just gave us yet another reason to love octopuses: RNA editing.
Normally we are stuck with genes the way they are delivered to us when sperm and egg unite. RNA editing is a cellular tool enabling genetic diversity but without changing the DNA. Scientists have recently discovered that octopuses, along with other cephalopods, the cuttlefish and the squid, use RNA editing extensively to customize their genomes unlike most other organisms studied to date.
The normal flow of genetic information is from DNA to RNA to proteins. Every cell contains an exact copy of the DNA obtained at conception, while the RNA and protein fluctuates based on cell type. Nerve cells produce different RNAs, and ultimately proteins, than skin cells.
Our genes are encoded in the DNA by a sequence of four molecular building blocks (nucleotides A, C, G, and T). DNA is normally faithfully copied into the RNA, so that you can predict a protein based on the DNA sequence.
Octopuses, squid, and cuttlefish do something different. With the advent of whole genome sequencing, scientists discovered that RNA in cephalopods frequently did not match the corresponding DNA. A’s at specific sites are altered to G’s. Once the RNA is no longer an exact copy of the DNA, it potentially encodes for a protein that is slightly different. These changes in the RNA are driven by a special set of enzymes (ADAR; adenosine deaminases acting on RNA), but they are not unique to cephalopods.
We understand how the process of gene alteration can affect cells, particularly in the context of human cancer. In cancer, mutations occur in the DNA and are carried into the new cells after each cell division, usually with disastrous consequences for the organism. Editing at the RNA level mixes things up, but presumably to the advantage of the organism. The level of RNA editing taking place might even differ among the same cells in a tissue, and different versions of the same gene/protein may co-exist with an individual cell. And then the altered RNAs can disappear.
Most organisms to date have the capability to modify RNA, just not typically in critical regions of a gene. Where only 3% of human RNAs might contain an altered site, scientists found 80,000 to 130,000 edited sites in octopus RNAs with over half of them (65%) leading to a new protein sequence.
Not all cephalopods use RNA editing to change proteins. In the more primitive cephalopod, the chambered nautilus, edited sites appeared in RNA transcripts at orders of magnitude less. Octopuses, cuttlefish, and squid split from the nautilus over 400 million years ago, so the use of the process was an attribute adopted during their evolution into a more advanced invertebrate.
Octopuses enchant us. They are quiet, and move gracefully through the water transforming to frighten us or to disappear into the environment. They slip through small holes, mimic other organisms, and screw off the lids of glass jars. Their brains are anatomically large, containing five times more neurons than a mouse, and they have some capacity for long term memory (weeks not minutes). Is RNA editing behind their sophisticated behavior? Scientists are entertaining that possibility. A large number of the RNA edited sites (11 to 13%) occur in genes expressed in neural tissue.
No clear explanation exists for why cephalopods embraced this mechanism of gene alteration over others during evolution. Octopuses already have large genomes so it does not appear to be a case of diversifying a small genome. Scientists believe that RNA editing allows these animals to adapt to more diverse environments. Temperature, for example, has been shown to both stimulate and inhibit RNA editing. But any environmental change you can dream up, the amount of sunlight or acidity, for example, might have contributed to the evolution of their dependence on RNA editing.
The ability to adapt or to acclimate to a changing environment would enable them to survive and perhaps equally as important, to mobilize! Indeed, nautiluses are more restricted in their habitats, typically remaining deep in tropical waters and only coming close to the surface in cooler areas. Octopuses are dispersed throughout the world in extreme habitats. You can find them in the warm waters of the tropics, the nearly freezing waters of the Arctic and Antarctic regions, and even near volcanic vents.
Maybe you are wondering what is the point of studying an obscure molecular process such as RNA editing. It is fascinating first of all, but such scientific studies are also relevant to how other organisms of potentially more immediate concern tolerate fluctuating marine environments. Corals, for example, are suffering tremendously under temperature increases occurring worldwide. Yet, some thrive in environments that normally cycle through extreme temperature variation over the course of a single day. Coral bleaching is a result of the loss of the coral symbiont zooxanthellae with rising temperature. The symbionts of corals existing in such environments have also been shown to use RNA editing in some critical genes.
There is a price to pay for the ability to alter genes “on-demand.” The cell machinery involved recognizes sites to be edited but under strict parameters. Regions near edited sites remain highly conserved in DNA, indicating that there is less leeway for the incidental change that might lead to evolutionary progress.
The octopus, the cuttlefish, and the squid might exist in a sort of suspended evolution.
But cephalopods have been on Earth a long time before us. Although their dependence on RNA editing may now limit their ability to further evolve, it’s possible they are better prepared to survive catastrophic change. Maybe cephalopods will outlive us all on Earth and be the ones to look back on a time when humans existed…
©Janice Marie Nigro/www.janikiInk.com
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