How We Mutate

Mutant Monica.png

Hmm, must have subbed in an adenine somewhere.

A few months ago, I read an article explaining that geneticists have recently found an important difference between humans and octopi. They have eight limbs! Weird, huh?

No, OK, the real discovery was that octopi and squids both adapt to their environment in a completely different way from humans. They can change physical characteristics quickly, thanks to the process of RNA (ribonucleic acid) editing. RNA provides the instructions for assembling the proteins that keep our cells functioning and regulate all kinds of cellular properties, and editing those instructions is a quick way to react to current stimuli.

How is this so different from how the human genome changes over time? Basically, RNA editing changes the octopus’s proteins, which express the genes encoded in the octopus’s chromosomes, at a pretty late stage in the game. Humans are used to significant changes to our own gene expression happening at an earlier point, in our DNA rather than our RNA. (RNA editing happens for us too, but it’s much less common and usually doesn’t even affect our proteins.) Here’s how our DNA mutates, in contrast to cephalopods’ RNA editing:

DNA is made of two long strands of nucleotides (distinguished by the four bases adenine, thymine, guanine, and cytosine) that bond adenine to thymine and guanine to cytosine, creating a ladder that spirals to form the characteristic double helix. To copy DNA, the two strands of a helix have to unzip, leaving the bases on each side free. There are a bunch of free nucleotides floating around, and once the DNA strands are free, they bond to their opposite nucleotides on both strands, ending up with two DNA helices.

Normal DNA Copying

RNA is copied from DNA in the same way, except that afterward the new chain frees itself from the DNA to strike out on its own. (Don’t worry, the DNA gets back together in the end.) There are several kinds of RNA, but we’ll focus on messenger RNA, which carries the instructions for the protein structure.

Messenger RNA carries the same information as the DNA it copies, but it’s only one-sided, so it doesn’t have the cool double helix shape going for it. I like to imagine it in fun ways, though.

Rejected DNA Illustrations

RNA just isn’t complete without U! (It stands for uracil, which appears in RNA strands wherever thymine would in DNA.)

The messenger RNA scoots on over to a ribosome, where there’s even more RNA already waiting for it. Transfer RNA comes in many varieties, each of which binds to a different amino acid. With the help of a third kind of RNA, ribosomal RNA, transfer RNA recognizes and binds to the messenger RNA in small chunks of three bases each, called codons. The codons each correspond to a specific amino acid, and the transfer RNA that matches any given codon binds only to the appropriate amino acid. Ribosomal RNA helps the amino acids bond together in a chain, which gives us a protein!

This is where problems start to become obvious, as the finished protein product reveals any errors that have crept into the DNA. Here are some examples of point mutations (the most common type of DNA mutation), with the copied, mutated strand on the bottom. I’ve labeled the amino acids that would correspond to the three-base codons when they show up in messenger RNA, so we can see how the protein itself would change for each type of mutation.

Silent Mutation.png

Silent mutations are harmless, because the single base change doesn’t change the amino acid (here, valine is still valine). With twenty naturally occurring amino acids and 64 (43) possible combinations of the four bases in our three-base codons, most amino acids have multiple codons assigned to them (as many as 6!), so it’s possible to get the same protein even with a mutation.

Missense Mutation.png

Nonsense Mutation.png

Missense and nonsense mutations are also single-base changes, but they do affect the protein. A missense mutation just substitutes a different amino acid, but a nonsense mutation uses one of the codons that signals a stop, so it cuts the whole protein short.

Frameshift Mutation.png

Frameshift mutations happen when a base gets missed or added accidentally. As you can see, this throws off the whole sequence because the codon groupings are all wrong, giving different amino acids all the way down the line.

All these mutations usually occur in DNA copying (though RNA mutations can occur, it’s much rarer), and unless they’re fixed, every messenger RNA that comes from that messed-up DNA strand in the future will carry a mutated code. Not only that, but without correction there’ll be more mutated DNA copied as well.

This is a fundamental difference between the way our genome changes, through DNA mutation, and the octopus’s RNA editing. DNA mutation is slow but permanent, and it opens the way for cumulative changes. RNA editing gets the specific job done quickly, but the same features that let the octopus edit RNA so readily also make the DNA sequences much more rigid. They can change in the short term, but they’ll always revert to the base proteins afterward.

Cephalopods are generally really interesting, and this recent understanding of their gene expression gives us more insight into our differences, as well as their fascinating features and abilities. Check out a nice summary of the RNA-editing research and, for more on cephalopods, here’s some general information and a cool article about an octopus-inspired robot!


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