The worst take on that cephalopod RNA editing story yet

That article I wrote up today? Take a look at the colossal botch phys.org made of it.

How octopuses, squid, and cuttlefish defy genetics’ ‘central dogma’

Jesus fuck, how can you write for a science news site and get everything that wrong? The central dogma of molecular biology (not genetics, dinglepoofs) says that the information in proteins can’t be written back into DNA. This study doesn’t even try to address the central dogma, much less “defy” it.

Now look at this paragraph. There’s a misplaced quotation mark in there, so I’m not even sure what part is actually the words of the biologist. No, not all information is stored in DNA. The RNA editing part is not new, not surprising, and isn’t going to surprise any knowledgable biologist (the degree that some cephalopods exploit RNA is unusual, but it’s not in itself revolutionary), and most definitely does not invalidate Crick’s central dogma.

In fact, RNA editing is so rare that it’s not considered part of genetics’ “Central Dogma.” “Ever since Watson and Crick figured out that genetic information is stored in DNA, we’ve had this view that all the information is stored in DNA, and it’s faithfully copied to another molecule when it’s used—that’s RNA, and from there, it’s translated into the proteins that do all the work. “And it’s generally assumed that that’s a pretty faithful process,” explains study co-author Joshua Rosenthal, a cephalopod neurobiologist at the Marine Biological Laboratory in Woods Hole, MA. “What the squid RNA is showing is that that’s not always the case—that, in fact, organisms have developed a potent means to manipulate information in RNA.”

I’m not even going to begin on all the news stories crediting cephalopod intelligence to this process.

Cephalopods are natural-born editors

Did you know cephalopods may have traded evolution gains for extra smarts? I didn’t either. I don’t believe it, anyway. The paper is fine, though, it’s just the weird spin the media has been putting on it.

The actual title of the paper is Trade-off between Transcriptome Plasticity and Genome Evolution in Cephalopods, which is a lot more accurate. The authors discovered that there’s a lot of RNA editing going on in coleoids. The process is not a surprise, we’ve known about RNA editing for a long time, but the extent in squid is unusual.

RNA editing is basic college-level stuff, so if your experience in biology is limited to high school classes or pop press summaries, you may not be familiar with it, so a quick summary follows.

There is a small family of enzymes in vertebrates called the ADARs, or Adenosine Deaminases Acting on RNA. These enzymes bind to double-stranded RNA, and convert the adenosine bases to inosine. Inosine preferentially base-pairs with cytosine, so this functionally converts the As in the double-stranded stretch into Gs.

There are limitations on this enzyme, so it doesn’t charge off and convert every A in every RNA into a G, which would be lethal! Since it only works on double-stranded RNA, which requires that the sequence of the RNA be such that it can fold back on itself and create regions where long bits of the sequence are binding to itself, it only works on some RNAs. This requirement also means that in some ways it is evolutionarily and genetically fragile — mutate a base somewhere in that dsRNA stretch, and it stops being double-stranded, and the enzyme no longer converts A to G.

Before the creationists and ID creationists get all excited, this is not revolutionary, and does not in some way preclude evolution. The presence of these enzymes means that there is an alternative way to tweak some bases in a sequence other than by directly modifying it by mutation in the genome. In a simplistic way, you can just think of it as another way a single-base pair mutation can occur — it’s just done in the transcriptome, rather than the genome.

It also has some advantages. Because the enzyme is not perfect, some RNAs escape the modification, which means the organism can have both the unedited and edited forms of the protein — so if the unedited form performs some useful function, that function hasn’t been eliminated in one swoop. It may provide a kind of soft transition between two forms of a protein.

There is also a disadvantage. Because the formation of double-stranded RNA requires the maintenance and cooperation of multiple bases in multiple regions of the sequence, coming to rely on RNA editing for one base can lock in the sequence of multiple other bases. That’s the meaning of the title of the article: the tradeoff is that yes, you can get a useful adaptive modification by modifying the transcriptome (transcriptome plasticity), but if you’re dependent on that, you’ve also limited the amount of change you can tolerate in associated regions of the genome (genome evolution). There is basically a window around the change you want that is approximately 200 bases long that you now have to constrain in order for your key change to continue to work.

That’s limiting. The authors point out that only about 3% of human RNA messages are recoded by ADARs, and only about 25 total are conserved across mammals. That implies that a lot of the RNA editing going on is spurious, but some tiny part of it is functionally necessary.

In contrast, some cephalopods, the squid and octopuses, have many more.

The authors searched for non-synonymous sequences between RNA and DNA. They found lots, and further, the A-to-G mismatches, which is what you’d expect if this were a result of ADAR editing, were greatly enriched. Most importantly, they compared multiple species, and only the coleoids exhibited this pattern, while Nautilus and Aplysia did not. This is a property of the organisms, not an artifact of their methods.

So how many sequences are modified by ADARs in squid? That’s tough to determine, since we know there will be spurious editing all over the place, but we can say confidently that it’s orders of magnitude more than what is seen in humans. The most relevant and conservative estimate in the paper is that “1,146 editing sites (in 443 proteins) are conserved and shared by all four coleoid cephalopod species”. Compare that to the 25 in mammals.

Also interesting is that the sequences identified are often developmentally and neurobiologically significant. Protocadherins (molecules involved in cell adhesion, and therefore important in the development of multicellular animals) were enriched both in overall number and in RNA editing sites. They also specifically compared the function of neuronal channel proteins in both the edited and the unedited versions. The unedited proteins were still functional, but the edited versions were more sharply tuned in their electrical properties.

Here’s an example. They recorded the potassium current for unedited K+ channels on the left, and for edited channels on the right. These are conserved editing sequences maintained in squid, cuttlefish, and octopus, and you can clearly see that editing removes differences between those species to produce a more similar pattern of current flow.

Conserved and Species-Specific Editing Sites Affect Protein Function Unedited (WT) and singly edited versions of the voltage-dependent K+ channels of the Kv2 subfamily were studied under voltage clamp. (B) (i) Tail currents measured at a voltage (Vm) of −80 mV, following an activating pulse of +20 mV for 25 ms. Traces are shown for the WT Kv2.1 channels from squid, sepia, and Octopus vulgaris. (ii) Tail currents for the same channels edited at the shared I-to-V site in the 6th transmembrane span, following the same voltage protocol.

Conserved and Species-Specific Editing Sites Affect Protein Function

Unedited (WT) and singly edited versions of the voltage-dependent K+ channels of the Kv2 subfamily were studied under voltage clamp.

(B) (i) Tail currents measured at a voltage (Vm) of −80 mV, following an activating pulse of +20 mV for 25 ms. Traces are shown for the WT Kv2.1 channels from squid, sepia, and Octopus vulgaris. (ii) Tail currents for the same channels edited at the shared I-to-V site in the 6th transmembrane span, following the same voltage protocol.

That we’re seeing changes in nervous system activity is probably why the first article I cited seems to think this has something to do with making cephalopods smarter. It doesn’t, directly. It’s more that one of the mechanisms driving the cephalopod radiation after the Cambrian was adoption of modification of the transcriptome via RNA editing. It’s a pattern that isn’t easily reversed — a lot of proteins would have to be tweaked at the genome level to make them independent of ADARs — but it works, so there’s no particular pressure on them to modify the mechanism.

Liscovitch-Brauer, Noa et al. (2017) Trade-off between Transcriptome Plasticity and Genome Evolution in Cephalopods. Cell 169(2):191-202.

Tooting Mastodon

There’s a lot to despise about Twitter, but at the same time, it’s become one of those social necessities, like those calling cards you had to have handy when visiting Victorian homes. But at the same time, Twitter totally sucks. It’s a haven for Nazis and shit-posters and harassers, and Twitter management has zero interest in making it better for users. Another problem is that they don’t seem to have any competition.

So let’s see some! Sarah Jeong explains a promising alternative called Mastodon. It’s similar in function to Twitter, but has a different underlying philosophy, relying on distributed clusters of users called instances, which then share conversations with users you follow more widely. I haven’t figured out all the mechanics yet, it’ll take time. The big difference is that the instances have zero tolerance for fascists, racists, and harassers, and they say so — and they’ll cut you off if pull any of the crap that is routine on Twitter. That sounds good to me!

If you’re interested in trying it out, go to the list of instances and pick one out — they’re rated for their reliability and number of current users. Jeong signed on to mastodon.social, but that one is closed right now, so pick a different one — they should all allow exchanges between one another, so it shouldn’t make a difference, I don’t think. I chose octodon.social, just because something about the name appealed. Don’t know why. I also kind of liked the manager’s rules:

It should be similar to mastodon.social’s.
NSFW/any legal porn is allowed, but tag it as NSFW or make it unlisted or something.
Trolls are only allowed if they’re quiet; you can shitpost but not harass someone, and my threshold is pretty low.
I’m not Twitter, I’ll fuck up nazis and bullies for fun, and get an AI to do it if I get bored.
I’m your nice cyberpunk queen but I intend to keep this place decent and safe for everyone.

So now I’m signed up as [email protected]. I haven’t done anything with it yet — you know the general principle with any social medium, right? Listen for a while before blaring — but the environment seems pleasant, if a little more quiet. The problem with these things is that they require a critical mass of users, or they fall flat and die, so that may happen here, too.

Oh, and another problem: you don’t “tweet”, you…”TOOT”. Ugh. Why do the people who have the smarts to set up this kind of thing always have a tin ear?

Anyway, if you’d like to take a small step in disrupting the Twitter hegemony, try it out.

Good museum news!

The Bell Museum is in the process of getting a new building and moving, and is scheduled to open early in the summer of 2018 — it’s a fine museum that will be even better.

The new $64 milllion Bell Museum slated to open in the early summer of 2018 is under construction on the University of Minnesota's St. Paul campus, Thursday, March 30, 2017. The building will feature products sourced sustainably in Minnesota, including white pine from Cass Lake; granite from Morton; Iron Range steel, and bird-safe glass from Owatonna Scott Takushi / St. Paul Pioneer Press

The new $64 milllion Bell Museum slated to open in the early summer of 2018 is under construction on the University of Minnesota’s St. Paul campus, Thursday, March 30, 2017. The building will feature products sourced sustainably in Minnesota, including white pine from Cass Lake; granite from Morton; Iron Range steel, and bird-safe glass from Owatonna
Scott Takushi / St. Paul Pioneer Press

One thing of note is that the new building will be very modern, with lots of glass, and look! A natural history museum, unlike our local football stadium, actually cares about animals in the region and will have bird-safe glass windows!

See, Minnesota Vikings? It’s not that hard to respect your community.

Eyes in the sea

I was informed that a panel of judges had selected the top underwater photos for 2017, and the grand winner was a photo of an octopus — so clicked over and looked. I was a little disappointed, since I’d already used that photo before…as well as a couple of others. I guess that means I must have good taste and a good eye to spot quality images before they win awards, right? But maybe it’s just that they’re all fantastically beautiful, as any fool can see.

So go browse all the candidate photos — they’ve all also got a short summary of how the picture was taken, and judges’ comments. You’ll find that whales are popular subjects, as are closeups of fish, and shots of underwater wrecks.

Fabrice Guerin

Fabrice Guerin

Jean Trestin

Jean Trestin

The Southwest is going dry

A great story from Rebecca Solnit: the huge dams that were erected in the 1950s are failing. Not in a catastrophic sense, but in the sense that the water is going away, leaving them useless, due to a combination of aggressive consumption by humans (Las Vegas and Phoenix are going to face huge problems) and climate change — less rainfall, more evaporation. It’s not entirely a bad thing.

When the Sierra Club pronounced Glen Canyon dead in 1963, the organization’s leaders expected it to stay dead under Lake Powell. But this old world is re-emerging, and its fate is being debated again. The future we foresee is often not the one we get, and Lake Powell is shriveling, thanks to more water consumption and less water supply than anyone anticipated. Beneath it lies not just canyons but spires, crests, labyrinths of sandstone, Anasazi ruins, petroglyphs, and burial sites, an intricate complexity hidden by water, depth lost in surface. The uninvited guest, the unanticipated disaster, reducing rainfall and snowmelt and increasing drought and evaporation in the Southwest, is climate change.

So at the same time that Florida and all those coastal cities face inundation, the desert boom is going to die the slow death of dehydration. Don’t imagine that you’re living someplace where nothing will change, though; it’s going to hit us all.

The idea is that climate change doesn’t merely increase the overall likelihood of heat waves, say, or the volume of rainfall — it also changes the flow of weather itself. By altering massive planet-scale air patterns like the jet stream, which flows in waves from west to east in the Northern Hemisphere, a warming planet causes our weather to become more stuck in place. This means that a given weather pattern, whatever it may be, may persist for longer, thus driving extreme droughts, heat waves, downpours and more.

I wonder what the economic cost of shutting down the golf courses of Scottsdale and the fountains at the Bellagio might be? And then of course there are the unpredictable disruptive effects as millions of people living in a place temporarily made habitable by futile exercises in short-term hydroengineering find themselves having to migrate elsewhere.

Don’t come to Minnesota! We’re probably going to experience an arctic vortex now and then and plunge into the deep freeze for a month at a time, alternating with winters that barely happened (like this recent one), and overall we’re going to turn into Kansas North.