March 02, 2016 at 02:40AM

Today I Learned: 1) Unstructured proteins are not the same as denatured proteins. The term "unstructured protein" is a rather glaring misnomer. Unstructured proteins almost always have structure, and well-defined structure at that. The "unstructured" tag just means that they aren't made of standard protein building blocks like alpha helixes and beta sheets. One way to think of it is that if anyone but an experienced protein scientist/engineer looked at a snapshot of an unstructured protein, they wouldn't be able to tell whether or not it was denatured, because it wouldn't have any of the usual protein structural features, BUT if you looked at a million copies of that protein, it would always look more or less the same. A "denatured protein", on the other hand, truly isn't structured. Denatured proteins flop all over the place; if you looked a million copies of the same denatured protein, they would all have different shapes. Thanks to Jeanne Morin-Leisk for teaching me about unstructured/denatured proteins! 2) When inserting DNA into plasmid vectors, it's a good idea to run a control reaction that doesn't insert anything. This screens for whole, uncut plasmids contaminating your vector -- if your control transformation has a lot of colonies, that means you can expect a lot of your actual transformations to be uncut vector, not your actual construct. If you have just as many control colonies as experimental ones, then you probably don't have any good colonies and you don't need to bother screening. A caveat: Gibson reactions tend to produce a lot of colonies in control reactions, even when the main reactions work just fine. ...I realize that the above paragraph won't mean much if you haven't done cloning before. For those of you, the tldnr is: today I learned a potentially useful control condition to use when performing certain common cloning reactions. Also, to be clear, here and in the rest of molecular biology, "cloning" just means "making DNA from other pieces of DNA", and has nothing to do with copying organisms. 3) Mimiviruses! Mimiviruses are MASSIVE viruses that infect amoeba*. How massive? Well, they were thought to be bacteria for a long time, because they kind of look like bacteria under a microscope (they're between 400 and 600 nanometers across, depending on how you measure, which is about half the length of a typical E. coli cell). Mimiviruses (obligatory: mimiviri?) also have a LOT of DNA -- the mimivirus genome is more than a megabase, encoding almost 1,000 genes, which is significantly larger than some bacteria (though still smaller than most, to my knowledge). More interestingly yet, mimiviruses carry several genes for amino acid and nucleotide synthesis, making them significantly more self-sufficient than your average virus and arguably more self-sufficient than some parasitic bacteria (I'm guessing mimiviruses can replciate their own DNA, but they definitely don't have their own ribosomes, so they can't produce proteins on their own). Mimiviruses are a contentious topic among scientists-that-know-about-mimiviruses. There's a lot of question about how mimiviruses came to be -- are they descended from parasitic bacteria that gradually lost their cytoplasm and cell walls, developing protein coats in their place? Or are they viruses that incrementally incorporated host genes for metabolism to gain more and more functionality? Or was it a virus that independently evolved genes for metabolism? Some scientists even been claim that mimiviruses, along with other closely-related viruses, meet criteria for life** and should be considered a fourth domain of life alongside prokarya, eukarya, and archaea. Questions about evolutionary origins like this are very difficult to answer (as Mengsha Gong can attest!), and we will likely never definitively know how mimivirus came to be. * Appropriately enough -- things related to amoeba seem to have a weird habit of being disproportionately large. Check out Chaos carolinense. Also, how big do you think a typical amoeba's genome is? For reference, a human genome is ~6,000,000 base pairs, bacterial genomes range from a couple hundred thousand base pairs to tens of millions of bases, and flu viruses have about 14,000 base pairs. Take a guess. Now go look up the genomes of Amoeba dubia and Amoeba proteus (for those without the ability to look it up, my apologies, but this really is a better exercise if you have to look it up yourself than if I post the answer). ** Personally, I think *all* viruses should be considered "alive", but that's a personal crusade of mine and it's not like it matters anyway.

Edit:  A couple more things I learned yesterday but forgot to write down:

1) Mimiviruses have their own viruses. That's not the first virus-infecting virus I've heard of -- adeno-associated viruses, or AAVs, are human adenovirus parasites that only infect human cells also infected by adenoviruses. AAVs are among the most popular vectors for viral gene therapy right now, in part because they can't replicate on their own. I also learned that a virus that requires another virus is called a "viriophage", which roughly translates to "virus eater". 

2) It looks like mimiviruses have an immune system against their viriophages, which probably acts much like the CRISPR system of bacteria that has given us Cas9, which I've written about at some length in other posts. Seehttp://www.nature.com/.../crispr-like-immune-system..., if it's not behind a paywall.