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If i ask you to
To picture evolution
You probably picture like a bird's changing shape to crack ack a harder net right or fish sh growing shararper job
Exactly it's external
Yeah
It's obviousyou hohold your hhand or just measure with a rules
Yeah
You can actually see it
But today we're looking at a staggering data et from a wpaper in nature
That proves the most aggressive rapid evolution on earth
是的是的
Uh isn't happening where you can easily see it
No
It's not
It's actually happening inside the dark microscope of a twisting landscape of the gut
Yeah
I mean we're step in completely past the teeth in the jawline
Here to the reality of biology is that catching the prey is well
It's only half the battle right the evolution ary pressure doesn't just stop once the food to swallow in fact
You could argue that is where the chemical on cellular battle really begins
And to explore that hidden frontier
We're doing a deep dive into an incredibly dense pice of research
Today it focuses on twenty four hyperdiverse sichicled fish species from lake tanguanica and east africa plus one outgroup uh the niil toloopia is the the olopia
So our mission today alongside you listening is to figure out how evolution physically rebuilds the digest attract talah literally sell by harddwired sell just to squeeze ze every ounof sursurvial out of a shifting envivionment
A massive undertaken
It is in the start
I want to talk about the sheer scale of how they mapped this
Because i mean if you just grind up up efficient test
And you just get bibiological movier ah essentually
So how do you mapped the microscopic architecture across
嗯的 对的 好的
Two dozen wild species
Well you have to abandon that smooth approach entirely the researchers use a technique called single cell transcript omic okay impact
That of it so instead of looking at the bulk dna or rna of the whole organ
Which is
Is you an average they use microphillitics to isolate individual single cells like one at a time
Literally one at a time they capture one single cell in a microscopic drop
Let they break it open
But they didn't the aun a just from that specific cell
Wow and only of courcourse being the mesenger ger uh telly us it's is genes in that particular cell dn a or entily ly ell cell
But actly right by looking at the rna
You see what the cells actually doing not just what it has the potential to do wait
So they are doing this one cell at a time
Like entire dijust just tracor memely chanchanally
Yes
It's fully automa through highly the advance sequencing technology obviously
But they didn't just do a few that sequenced eighty two thousand
Six hundred and twenty indiindidual cells
Ls a ty thousand cell cell while to cross all these species yet
And by looking at the unique combination of genes turned on in each of those cells
They identified twenty four entirely distinccell populations just living inside the situlaand testing because
Because leveveof resreslution is i memean comcompleshttered the way
We visually think about a absolutely because if you look at human atomy
We have a stomach
We have small
Intesting and large and test
To have very obvious celsical popartment just distinct zones
Yeah
But a six like gut
If you just pull it out
Look at it
It's basically just a long plain too
嗯 Yet
This single cell data proves that internally structurally it is not a uniform
Two at all right the physical anatomy is completely deceptive
The cellular map reveals profound subfunctionalization
Along what we call the anior posteior access meaning the front of the back
Yes
Front of back
The front of the gut
The interior is fundamentally different
On a molecular level from the back
The postesteria okay
How are they different well in the the terior section
The tissue is heavily populated with a specific cell type
The researchers identified as enterroizze one contterroites one got it yes
Cells are essentially in microscopic fat processing stations
They are highly specialized turning on specific genes for lipid and small molecular metaboism alfrom fvisualizing this when a rather papapproh a factory assembly line hidden inside a really plain brick building
That's a great way to picture right from the street
It's just a long building
You think the whole thing does one job
The inside station one right by the loading dog is entirely dedicated to processing fans
And as you move down that assembly line to the back of the building
The poststerior
The entire cellular workforce turns over back there the tissue ppacked with what a called licous and rich and terrassites or lr es l ores and licesums
Being being little uh recycling centers or chemical stomachs inside a cell
Exactly the right way to think about them
Licisses are packed with lzythms designed to break down really complex molecules
So these lr es in the back of the gut are heavily specialized for protein absorption and the interest cellular gestion of complex proteins
Okay
So i want a pause here into a quick five military cap of what we''ve built so ar ar so these bullet point one
对对对
We know this siccad dt is heavily zoned ed internally
Even if it explained on the outside yep bloop point two
It's atts in the front with interterosites one and prokinins in the back with the illers
And having that to a questions of you the listener think about the engineering of it all
If you are designing a biological factory from scratch
Why might it be vastly more efficient to process
Because easily absorbed lilipids and small small lecules right right away at the front door
And then save the heavy duty ends
I'm intensive protein breakdown for the end of the line
It's a great engineering puzzle
Which having that invisible baseline map knowing exactly where these selelers supposed to live is what allows us to ask the next much bigger question
Because you 're basgly instatic
Exactly the researchers wanted to to know how millions of years of changing diet completely redrew that salular map
Which brings it a masass of logistical problem
Thethe're 're at a vast wild fish specispecithat eat wildly different things
Right right ah lge insex other fiit think even survive exclusively by biting the scales off of larger fish
Which is horrifying
But cool nature is brutal
It really is
But it's not like these wild seatuento have dietary food
Food gugs
How do we know what their ancestors have been eating for the last few million years
Well
The fish leave a permanent chemical signature in their own tissues through what are called stable icotopes
Ok
The researarchspecispecially iclooked at the ratioof nititrogen fifteen and carbon thirteen in the muscles of these fish
Let's unact the mechanics of that
Because stable icotopes are basically nature res receipts
好的 对的
But how does nitrogen fifteen actually tell you
If a fish is a vegetarian or a carnivar
It comes down to bioaccumulation nitrogan fifteen is a slightly heavier stable version of regular nitrogen right
And because a heavier it doesn't get exeeted from the body as easn't as lighter nitrogen does it sticks around
I say so an alg eater eats a plant
And takes on a baseline level of nitrogen fifteen
And when a carninivous fish eats that nitrogor
It inherits all that heavy nitrogen plus
Whatever it accumulates itself
So a concentrates heavily as it moves up the laatter
It concentrates very heavily
So the ratio of nititrogen fifteen
It they did know nthrotically as delt fiffifteen acts as a direct proxy for the fishous trophic lab meaning where they sit in teen chain
Exactly a low number means you're looking at it earr before because a high number it doesn't looking at an apex carnivore
Okay
What about the carbon thirteen meanwhile they use the carbon thirteen signature as a proxy for the fishous habitor
It distinguishes they feed down in the muck
Near the shore
The benthic zone
Or if they hunt out in the open water
The pilegic zone got it
So they compile these stable able yhotoproceeds to figure out
Exactly where the fish sits on the food chain othen they cross reference that with the factory assembly line
The single le cl lpp just talked about oand the correlation they found is massive
Right because the abundance of those fat processing cells in the front of the gut
The entire sicience and just skyrocket in the the carseverse fish
Yeah
The fish eating a high protein high fat meet diet
Have literally rebuilt their internal assembly line
They feature far more of these specific fat processing stations compared to the algidors
The carnivor is essentially expanded the first phase of their factory to handle the massive influx of complex animal lipids ds
That's exactly what happened okay
But i have to push back here just to play deouels advocates
Sure
How do we know this is actually hardwired evolution
嗯
Let's say i suddenly adopt a strict high fat keedo diet for six months right your body react
Exactly my body's going to react
My got temporarily a regulate certain anzymes
Or maybe even even just the cell ratios hand laall that extra facat
But if i switch back to etrtrfacs
It resets phannotipic plasstiticity
Right
So do the researarchers know this isn't shshterterm plasticity
是的是的
That the fish 's gut is just reacting to whatever it happened to eat that month in the lake
It's a crucial question and the researchers anticipated that exact critique
Which is why they didn't just rely on the rna expression levels of wild caught fish
Which like you said could flulutuate ate
So do they do do validated the actual physical architecture of the tissue
They brought in a much higher level of more phological evisuence using a techniqucalled flloresian atsetue hyoritizone fish essentially making the specific genes glow in the dark
Making the rna transcripts glow
Yes
They took a specific marker gene called m case one
And they ically aclike like a hming began exclusively for inteteriizone one
They designed a complementary probe attached to a flresent molecule one
They wasased this over the gut tissue
The probe chemically binds only to the m pace one rrn
And then
Then put
Put it under microscope and under microscope every single enteriide one physically lights up
They did the same thing with a gene called up to light up the protetary adsting sting aleries in the back okay
But how does a glowing cell prove it's a permanent evolution ary change
Couldn't there just be more glowing cells
Because the fish aa a avavmeal yesterday
That's
That's where comcomparative anatomy and lab controls come in
They controlled for diet in a laboratory setting
They raise them on uniform diets and the structural differences persisted anyway
I say it wasn't just that the cells were ququotite turned on more the actual physal proportion of the gut tissue dedicated to these cells was permanently altered the architecture is locked into their genetics
So it's not reaction
It's a blue print
Exactly the carniver species have evolved to maintain a much higher permanent baseline proportion of enteriizone
More the efficiently process high fat diets
And they often do this over much shorter overall gutlinks than the earb force okay
So it's do another quicicy cap
Let's do it
Bullet one
嗯
We track their diets using icototo proceeds the enterteen and sea thirteen
Bullet too we've found cartowartes have way more of these in terroriztes one right and bullet three
Thanks to the lab controls in the glowing fis imagging
Know this is a permanent evovoluary blueprint not a temporary diet fed perfectly summarized
So here's a question for you listening
Think about your own diet in your own ancestral history
If you're cellular make up shifted permanently based on what your ancestors date or generations
What specific kind of specialize cells
Do you think would dominate your digest attrack
Today it's a fascinating thought experiers
And to really understand how that permanent shift happens in the fish
We have to go deeper than the cell member we
We could look at the raw code
Yes
Because the dna instructions driving these enterroizes one are behaving very strangely compared to normal evolutionary rules
Right
So we are transitioning from the number of cells to the actual molecular mechanics inside the nucleus and the genes running these fat processing cells are absolutely rule breakers they really are
We was reading through these notes and trying to synthesize ze why specispecic genes mumutes so incredibly fast
I realized they all share three main trates actually started
Calling them the why sf cells in my head
Why sf yeah young specific and free
You know that framework actually maps perfectly to the genetic data in the paper oawesome
But to these reciate why being young specific and free matters we first need to define the rule they are breaking
Which is evolution ary constrainment okay
Explain that straraint usually genes
That control fundamental data day cellular functions are under strict stabilizing selection meaning if it works
Don't touch it
If a genis responsible for say turning oxygen into energy
The increommutation in that code is almost certainly going to be fatal
So that genetic sequence stays frozen over millions of years
Right stabilizing selection is biologies quality control
Yes
The single cell data revealed that the genes expressed in these enterisites one have incredibly high rates of sequence divergence across the different interleid species
They're mutrapitly the rapidly dly they are not for us at all
So let's apply that ysf framework to see how they get away with this rapid mutation age
Why is young g the the researchers measured this using a transcripomm age index or tai
How does that work by using an approach called philestrategraphy scientists can look at a dn a sequence and trace it back through the evolution ary family tree to see one
It first appeared like carbon dating for code sort of of yeah
Yeah
And they found that entire sized one rely heavily on evolution ary younger genes okay
So because these genes or relatively new additions
They haven't been deeply hard wired into those ancient life or death
Biological pathways we mentioned it's said it's like writing a new piece of software code for an app
You have a bit more lead al metric with it and break things without crashing the entire computers 's operating system that's a perfect anallogy
That's the why they yes is specifacfind the specific of measured by a mathematical metric called a toscores the genes driving the rapid evolution and entiosiztes one have very high tow scores
Which indicate more enetishee speciacity meeting
They aren't multi asking right
These genes are not being turned on in the fishous brain
Or it's hard
Or its skills they exist in functional ylusively in the end heior gut
And that extreme specificity sets up the f free free from pleattropic constraints
Yes okay we need to detail what pleattropy is
Pleattropy is a critical concept in genetics
Where one single gene controls multiple seemingly unrelated trades across the body okay so a gene operators and both the gut to digest food
Because the brain to immulate horoes mutating that gene to make digestion five percent more efficient
Might accidentally cause catastrophic neurological damage
Oh
Man
So that multtasking creates a massive evolutionary road block
Exactly
But because the enterriite one genes are so specific
They have very few protein
Protein interactions or p pps outside of their immediate local network
They are so operators
They really only do one job
And we know this freedom leads to actual functional changes
Because the researchers analyzed the dns raratio of these genookay
We need this ultirely explain the dnps ratio
Because as i understand it
This is the ultimate proof of active eevotion of this genes person of two different types of mutations
Right synonymous first is not synonymous right
Let's break down the mechanics of a mutation dna is read in three letter chunks called codons and each code on codes for a specific minoacoid
Right
But the code has redundancies
Sometimes if a single letter in the dna randomly mutates the new three letter chunk still cofor for the exact same aminoacid is before
So the end product doesn't change
Exactly the resulting protein doesn't change it all that is a synonymous or silent mutation
It's a type that doesesn't tually change the meaning of the word
And because it doesn't change the protein evolution
Basically doesn't care right doesn't help the fish
It doesn't hurt the fish
It just acts is a quiet background ticking clock of random chance over time
Exactly the mechanism
But a nonsynyyous ous mutation change ges the letter in a way that does alto the amino acid okay
So that physically changes the shape for the function of the resulting protein
Yes and the dnds ratio o simply compares the rate of those functional changes to the background ticking clock of silent changes
So what's normal in most genes
The ratio is far below one
Because functional changes usually break the protein and get wiided out by natural selection
But in these inteteriiite one ie the ratio is highly elevated
The rate of non synonymous mutations is outpaacthe the ackackground clock
Wow Yeah
That mathematically proves that natural selection is actively favouring function physical changes in these specific proteins okay
Let's bring it all together for another recap sounds good bullet one
对的对的
We move from the cellular er to the dn a layer bullelet too
These cells use the ysf rule
They could evolve rapidly
Because they utilize young highly specific genes that are free from the conststraints of multtasking in other parts of the perfect bulletry three eleelevated dnds ratio approves this evolution is active and functional 对不对
这的这个
So listener
Here's your question for this section
Do you have a highly specific single task tool in your kitchen or work space
Like aa dedicated apple core or a garlic press for a garlic press
Yeah
Notice
How much easier is to bend modify or completely replacthat one tool without disrupting your entire life
Compared to a multitool that you rely on to open cans tightenscrew ws and cut wires
That is exactly
What evolution is doing here
If a gene only does one job in one
Eself evolution can treat it like a laborator experiment right
But that freedom to experiment raises an essential question about the timeline
Well we know the cells change
We know the genes have the mathematical freedom to mutate 的
But how fast as this actually happen is this just a slow steady continuous drift over ten million years
What does the actual speed of this adaptation look like on a graph
It's not slow instedy at all to model the speed of trade evolution
The researchers applied complex mathematical models to the genetic data now usually normal random genetic drift is modeled led brobroonnian motion
Which is basically a random walk right like a drunkqured wandering around a field
Every step is random led a milmilliof years
They
They might ft far ar where they started
But there's no specific direction or pool
Exactly
But the gene expression divergence in these gut cells did not fit the browny emotion model at all the model that fit best was the orinstein olympic or ou process
Okay
Let t's act the the mechanics
The ouu process is it fundamently different from that random walk
And orinstein olympic process models ls system m as experiencing a random walk
But it's constantly being pulled toward a central optial state
Okay give me an analogy
The classic analogy is a rubber ban attached to a peg
If the environment is stable
The peg doesn't move
The rubberban allows a little bit of drift
But it keeps the organisms tretras relatively shift pulling them back
If they wander too far
But what happens
When the environment violently changes the peg moves
Owow yeah
If a fish enters a radically new environment
Say a tectonic shishift alters the lake
And the fish suddenly has to switch from a planant based diet to eating other fish
嗯
The optimal state for survival of rurutly i shifts
So the rubban stretches
It stretches to its absolute limit
And then it snaps the biology toward the new optimum
Very rapidly once it reaches that new optimum
The rubbbban's stabilizes again at the new pig
So it's not a slow steady ticking clock
It's an expsisive speat of intense evolutionary speed followed by a long pattoo stability
That's it exactly the data shows massive explosive bursts of accelerated evolution
The the spfific genetic pathways
The papapactually highlighted a specific group of six lens
The trophoni tribe
Where this is incredibly obvious
What have with the trophoni tribe about one point five to four million years ago
The water levels and the physical environment of lke tanenqua fluctuated wildly major new ecological nices just suddenly opened up chaos in the lake
Total chaos in response
The trophani tribe experienced a major puse of dietary diversification
As they rapidly switched back and forth between grazing on lg on rocks to hunting other fish
The ou models show massive birth of accelerated evolution in their enterrociite one genes
They were literally leaping across dietary boundaries
And their ysf cells were mutaating in adapting bipopulations to keep him alive
Yes
It shows that
When the ecological pressure is high enough
And the genetic conconstraints are low enough
Apaptation is explosive
It's perfectly time with the ecological shift
It perfectly allins the internal cellulumachinery with the external environmental chaos precisely okay
Finally recap before irap up
Yes
Oll let one yeah move from slow steady drift to the ou model through ever band bullet too the trophoni try drives that this happened in rapid bursts driven by egological chaos
So to the listener what environmental pressures in our world
Right now they be literally sudden rapid biological shifts in annual populations
Today it really makes you think about how dynamic life be is it's fascinating
And you know it really brings us to the core
So what of this entire data said
Why should you listening to this care about the mathematical mutation rates of african fishing tests
Right because this deep dive level that eep gengical apaptation doesn't just happen on the outside
It is multled layred
When an animal adapts to a new niche
It doesn't just slowly grow a sharper jaw over millions of years
When it literally rewrits its internal celluluworkforce it it deep genetic code simultaneously snapping towith a new optimm to survive the siitlegut tees us a hard biological role tissues must adapt at the cellululevel to handle must adapted new nutritional profes es it we take that rule and appplay to our own species
Well it leaves us with a rather profound almost unsettling perspective
Because our dietarienenronment ment has just experienced a massive violent shift now sider the time scale
This fish experienced explosive genetic burst over thousands of years
Just to digest algie versus fish scales now look at the human diet over just the last hundred years
So Oh Yeah
We have introduced a staggeramount t of ultraprocessed foods
Refined dense sugars and novel chemical and molcifiles
That are ancestors never ever encountered nature are have completely this deep ically change the fuel
We are putting on to our own internassembly line
We move the pig in the ou model
We move the pig
So if this speciually teaches us that survival requires racid celilillar adaptation of to new diwhat what invisible volulutionary pressures
We incompletly putting on our own terrorisites
Right now our human guts currently elgoing ted to burst of accelerated to scene evolution to hhandulultraprosites food
And if they are what of the biological cost of that forrest apaptation it's it completely flips
How you look at the body
We started this deep dive
Talking about how much we love clear visible x rays of a broken arm
We like evolution
When it's a birds speak
We can point out in measure
It's easy underststbut our real story
The deepest mechanism of survival is happening in the dark
It is happening in the microscohic muddy waters of the gut
Where cells are quietly shapshishifting muting and snapping to new optimums just to keep us life
The most powerful changes in nature are almost
Always the ones we cannot see with the nakked eye
I couldn't said it better take a moment to think about your own internal assembly line
Today
Thanks for joining us on this deep dive
Keep questioning what's happening in the dark
