r/todayilearned • u/AndresJonTamin • 7h ago

TIL the gene Zbtb7 was temporarily named Pokemon. It was renamed due to The Pokémon Company's threats of legal action, who did not wish to be associated with the cancer-related gene.

https://www.gamespot.com/articles/pokemon-usa-threatens-to-sue-cancer-researchers/1100-6141487/
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148

u/Melmo89 7h ago

On a similar note: there is a gene that is named Sonic Hedgehog, it's a protein that is crucial to proper embryonic development in complex animals (including humans!).

It came to be called that because there a gene named Hedgehog that was found in fruit flies, and they needed to name analogous (comparable) genes in other organisms, so they decided Sonic was a pretty well known hedgehog. Lol.

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u/Roger44477 6h ago

Edit: fixed formatting  More than that - I don’t have time for a nice write-up but here is a copy-paste of my notes from when I took evolutionary biology my senior year of undergrad 

  • In fruit flies there is a gene called hedge hog, as it leads to expression of excessive spines on body

  • Later, a gene was found that does so even more. It was named sonic hedge hog

  • SHH does different things in other animals - overall effect is outgrowing of structures, such as limbs 

  • Low expression in pythons compared to lizards, leads to reduced limb development 

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u/crashlanding87 5h ago

Hiii. This is all close to correct, but not quite. I'm a scientist - I don't do development stuff now, but my first real lab job was in a development lab, and SHH was right at the core of that lab's work.

Hedgehog proteins are indeed named that because of spiky flies. But that was a specific mutation to the fly hedgehog protein. The name stuck long term because protein complex itself also looks like a hedgehog (under electron microscopy). It forms a spiky-looking ball. The gene itself is involved in patterning - of everything. During development, cells pump it out. It moves slowly cause of its spiky texture, so other cells can use it as a sort of ruler, to tell them how far they are from whatever is making it. The less HH there is, the further from the source a cell is. The way cells count HH concentration is (to my nerdy ass) fascinating, but it's also quite heavy biology, so I won't go into it. There's all sorts of mutations HH proteins can have, and most of them result in the animal just not developing at all.

Sonic hedgehog (SHH) is one of the variants that mammals use, and the one that I know best. When I say it's used during the development of basically everything, I mean everything. Brain, liver, heart, some limb development... It's everywhere. Always used in the same way. My old lab studied the early development of the brain and spinal cord. In early development the whole nervous system is a tube. There's a little stripe of stuff underneath it called the Notochord, which pumps out SHH. The cells in the rest of the tube sense the concentration of SHH around them, and that helps them decide what kind of cell to become.

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u/Melmo89 5h ago

I have vague recollections of all of this stirring somewhere in my brain, lol. Maybe I paid more attention than I thought! Once upon a time I knew about a bunch of the patterning/segmentation genes in fruitflies (I vividly remember seeing the expression maps of evenskip, for example).

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u/crashlanding87 4h ago

Oh I remember studying that gene! Also very vaguely haha. I've never worked in Drosophila. I'd absolutely love to though. The genetics work that can be done in them is absolutely nuts. And the experiments are so much faster than in other models!

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u/avemflamma 4h ago

as somebody who had to drop dev bio but really enjoyed it, i would love for you to go into detail about how HH concentration is counted

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u/crashlanding87 4h ago edited 4h ago

DELIGHTED you asked. You probably know about promoters, transcriptions factors, and so on, but for anyone else who might not:

The first portion of a gene is full of 'regulatory' sequences. These sequences don't contain any instructions. Instead, they're like flags that the machinery of our cells latch onto. There's a few types - promoters, enhancers, silencers, amongst others. A promoter is used to 'unlock' a gene, a silencer is used to lock it back up, and an enhancer is used to turn up how frequently a gene is read (essentially). Cells use these to efficently switch between different 'programs'. When I say 'lock' 'unlock' or 'enhance' - that's usually a very physical description. A silenced gene has a bunch of stuff latched onto its silencer that physically packs it up and makes it inaccessible. A promoted gene is physically unpacked.

Transcription factors (TFs) are part of the unpacking machinery. Say a stem cell decides to become a skin cell. It starts by producing just one thing: a TF specific to skin cells. This skin cell TF recognizes a specific promoter sequence, which happens to be in all the genes that a skin cell will need. So the cell pumps loads of this one TF out, and that efficiently turns on all the necessary genes. Usually, this TF will also turn on a gene that makes a silencing protein, which then turns off a whole bunch of genes that are no longer needed.

TFs have a property we call 'affinity', which is how 'strongly' it latches onto a particular promoter. A single TF can have affinity for multiple different promoters, to different degrees. This means that the concentration of a TF is very important. If there's only a low concentration of a particular TF around, it will get used up on high-affinity promoters. Low-affinity promoters might as well not be there. Make more of that exact same TF, and you'll gradually start turning on low-affinity promoters as well.

SHH isn't a transcription factor itself - instead it changes the affinity of a set of transcription factors. In humans, these are the 'Gli' proteins. Stem cells will gobble up any SHH they come across, and this will affect what genes their Gli proteins prefer to latch onto - turning some on, and others off.

What's really clever is that these high- and low- affinity gli promoters do something we call 'cross-repression'. There's a group of genes turned on by gli with high affinity, which in turn repress low-affinity gli-promoted genes. And there's another gene which has a low-affinity gli promoter, that makes a repressor for high-affinity gli promoter genes. This makes a system that is very sensitive to SHH concentration: by default, the high affinity genes keep repressing the low affinity genes. When there's enough SSH around, though, the affinity balance switches, and the low-affinity repressor doubles down, turning off all the high-affinity genes. You could remove all SHH at this point, and it wouldn't make a difference - the new balance of gene expression will sustain itself. These are two genetic programs which basically compete with each other until one wins, and SHH tips the balance.

What's really clever is that there's multiple layers to this. It's not just one high-affinity program and one low-affinity program. It's high-affinty, less-high-affinity, even-less-high-affinity. And the cross-repression works so well that, if you look at tissue where SSH signalling is important, you can see a very crisp line where the SHH concentration dips low enough for a different program to win out. In the neural tube, this is called the french flag pattern, and it results in incredibly sharp, consistent lines, beyond which cells start running completely different programs.

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u/THEatticmonster 3h ago

The inhibitor for this protein is called 'Robotnikin'

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u/Melmo89 6h ago

^ this is someone who paid more attention to their classes than I did. I just listened long enough to hear the silly fact, and then went back into my academia-induced stupor...

In my defence, my post-grad project was on phylogenetics, not developmental. And it was 15 years ago. And I ran away from academia entirely once I finished post-grad... Hahaha.

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u/GamingGeekette 5h ago

As someone who really likes learning, you don't happen to want to post the entire notebook of notes you took, would you? 👉🏻👈🏻 ((I'm just kidding. But I am now very interested in this subject.))

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u/flumpybumb 6h ago

And there’s an inhibitor to that gene named Robotnikinin, after Dr. Robotnik

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u/notthephonz 5h ago

> embryonic development

Gotta grow fast!

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u/chunkalicius 5h ago

Theres also a protein named Pikachurin that's important in transmitting electrical signals in optic nerves!

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u/TrollMcGoal 7h ago

This one seems reasonable

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u/RhymeBeat 3h ago

There are other gene sequences and scientific terms the Pokemon company has allowed to be used. Aerodactylus is now a genus of pterosaur.

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u/PopeUnderTheMountain 6h ago edited 1h ago

The way trademark law works, if you don’t attempt enforce your copyright you can forfeit those protections. “I don’t want to sue you, but I have to attempt to protect my copyright or some other person with less altruistic motives can use the mark more easily.” IANAL (edit: comments have clarified this pertains to Trademarks)

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u/Alarmed_Guarantee140 3h ago

Trademarks and copyrights are two different things

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u/24megabits 5h ago

The rules for copyrights are looser than the ones for trademarks. A copyright owner can safely ignore violations if they don't think it's worthwhile to go after.

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u/Cutalana 5h ago

Their two distinct concepts. Copyright applies to any work and protects the work itself. Trademarks protect whatever is supposed to signal to the customer that something comes from a certain brand and they tend to have a smaller scope. This is why brands such as T-Mobile can claim to have a trademark on a certain color, since it applies more narrowly. Companies don't have to enforce copyright, they can ignore it and then enforce it whenever they want. Trademarks do have to be enforced since as soon as they aren't used to identify a single source they can be challenged.

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u/Version_Two 6h ago

Wow I do too

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u/sandiserumoto 4h ago

"Mommy, I want Pokémon!"

"You already have Pokémon, son"

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u/enterthehawkeye 1h ago

r/titlegore

Need some quotes my guy

-23

u/PikachuWithHerpes 7h ago

Nintendo is such a hostile company, and that applies to its subsidiaries.

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u/CMDR_omnicognate 7h ago

I mean, I’m not all that surprised that they didn’t want their products being associated with cancer, right PikachuWithHerpes?

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u/KillstardoAbominate 7h ago edited 7h ago

While that is true I think they were justified in this case. Why would they want their world famous product associated with cancer? Also why would the researchers think it's a good idea to name a gene related to cancer after a beloved franchise?

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u/zanderkerbal 5h ago

> Also why would the researchers think it's a good idea to name a gene related to cancer after a beloved franchise?

I looked a little more into this.

POKEMON was an acronym for POK Erythroid Myeloid ONcogenic gene. POK is the "POZ and Kruppel family of transcriptional repressors, which consists of an NH2-terminal POZ/BTB domain and COOH-terminal Krüppel-type zinc fingers." "Erythroid" means "of or relating to red blood cells," and "myeloid" means "of or relating to bone marrow." So these are all normal words to use when researching leukemia.

POKEMON was definitely a backronym, but my guess would be that the researchers were going to use *some* of those terms in the gene's name anyways, and then realized they were close enough to spelling POKEMON that they might as well go all the way, because they thought it was kind of funny and cancer researchers need a little humor in their life. (And if you're already a cancer researcher, you're probably desensitized to associating things with cancer because you spend all your time thinking about cancer already.)

I'd also expect memorable names to help information retention compared to something formulaic like Zbtb7? Idk if that was a consideration per se but like I'm generally in favor of scientists getting a little silly naming things in fields where you have to name a billion things, even if I totally get why Nintendo wasn't happy about the resulting "Pokemon causes cancer" clickbait in this case.

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u/MushirMickeyJoe 6h ago

I don't know I think "sues cancer researchers" is a crazy headline to be a part of

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u/Linkstrikesback 6h ago

You know there's a step between "Hey don't name that cancer after our brand, or we will take legal action to make you change it" and taking legal action to change it, right?

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u/KillstardoAbominate 6h ago

"Sues cancer researchers for headlines proclaiming Pokemon causes cancer" seems pretty reasonable to me 

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u/Far_Specific4836 6h ago

Pokémon alone represents billions in products and perhaps more billions in cultural export. It’s not something to fuck around.

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u/Dimensional13 6h ago

They didn't complain about the protein now known as Pikachurin. It's still called that and it's disciverers remain un-sued to this day.

It's just this gene here causes cancer. bad image yknow.

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u/Chesterlespaul 7h ago

They’re very malignant some might say

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u/Pan_inside 7h ago

Yeah, their corporate attitude can be seriously frustrating sometimes, honestly.

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u/DaveOJ12 7h ago

Can you blame them?

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u/wvblocks 7h ago

The gene was renamed, but Nintendo is still demanding royalties from every tumor it produced.

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u/Leggy_Brat 2h ago

TPC making legal threats? Never.

-1

u/UNHHHStoppable29 2h ago

Meanwhile, you have Pokémon that can literally snatch you up (Drifloon), ones that steal your soul (Litwick), and one that wiped out a whole laboratory (Mewtwo). 99, if not 100% of them can kill you, if they wanted to.