Before animals first walked on land, fish carried gene program for limbs

Jul 11, 2011
A genetic switch taken from the skate activates a marker gene in the distal limb of the mouse embryo. Credit: Igor Schneider, University of Chicago

Genetic instructions for developing limbs and digits were present in primitive fish millions of years before their descendants first crawled on to land, researchers have discovered.

Genetic switches control the timing and location of . When a particular switch taken from fish DNA is placed into , the segment can activate genes in the developing limb region of embryos, University of Chicago researchers report in . The successful swap suggests that the recipe for limb development is conserved in species separated by 400 million years of evolution.

"The that drive the expression of genes in the digits of mice are not only present in fish, but the fish sequence can actually activate the expression in mice," said Igor Schneider, PhD, postdoctoral researcher in the Department of Organismal Biology and Anatomy at the University of Chicago and lead author on the paper. "This tells us how the antecedents of the limb go back in time at every level, from fossils to ."

The genetic hunt was inspired by a famous find – the 2004 discovery of the transitional fossil Tiktaalik in the Canadian Arctic by a team led by Neil Shubin of the University of Chicago. A transitional species between fish and the four-legged tetrapods, Tiktaalik possessed fins containing a skeletal structure similar to the limbs of later land-dwelling animals.

Those similarities – particularly the wrist and hand-like compartments present in the fins of Tiktaalik and its peers – inspired a laboratory experiment to look at the homology, or shared physical and genetic traits, of fish and limbed animals.

"This is really a case where knowing something about the fossils and the morphology led us to think about genetic experiments," said Shubin, PhD, the Robert R. Bensley Professor of Organismal Biology and Anatomy and senior author of the study. "Tiktaalik and its cousins showed us that this limb compartment is not an utter novelty in tetrapods, as was thought for a long time. So an antecedent of that program must exist."

The research team compared a genetic switch region called CsB, known to regulate limb development in humans, with similar regions in mice, chickens, frogs, and two fish species: the zebrafish and the skate. Because the last common ancestor of all these species pre-dates Tiktaalik-like "fishapods," the comparison offered a glimpse at biology before animals made their first steps on land.

Genetic instructions for developing limbs and digits are shared by species separated by 400 million years of evolution. Credit: Kalliopi Monoyios, University of Chicago

Schneider and colleagues compared the CsB regions from all five species and found that certain sequences were shared between the fish species and the tetrapods. The conservation allowed the researchers to try swapping switch sequences between species to see if they could still drive gene expression in the fin or limb. Remarkably, mouse CsB could turn on gene expression at the outer edge of the developing fin region of zebrafish, and both skate and zebrafish CsB were capable of activating gene expression in the wrist and proximal digits of the mouse limb.

"These sequences function in these organisms despite 400 of separation," Schneider said. "The homologies that are perhaps not evident by morphology – just comparing a hand and a fin – can be traced back to the genome, where you find that the regulatory regions that control the making of those structures are actually present and shared between these organisms."

The results contradict a previous finding that a developmental switch from pufferfish DNA was not capable of gene expression in the limbs of mice, suggesting that tetrapods evolved a novel developmental system. But the new experiments suggest that the genetic switch controlling limb development was in fact present deep in Earth's evolutionary tree.

"There previously was the idea that these switches had to be generated from scratch de novo, but no, they already existed, they were already there," said Marcelo Nobrega, MD, PhD, assistant professor of human genetics at the University of Chicago Medical Center and another author of the study. "Maybe the key was expressing a gene earlier or later or in a specific territory, but it was just a modification of a program that was already encoded in the genomes of fish almost half a billion years ago and remains there to this day."

"These new results are actually in line with both the fossil data and the expression data," Schneider said. "So now we can tell a story where the fossils and gene expression make sense in light of the genetic regulation."

Future experiments will focus more closely on how the gene regulation system functions, examining the differences between the segments in and tetrapods that control development of either a fin or a limb. Subtle changes in the timing or location of may produce the dramatic differences in anatomy that first allowed animal life on Earth to explore land.

"There is a whole universe of questions that are opened up by this discovery," Shubin said.

Explore further: Big-data analysis reveals gene sharing in mice

More information: The paper, "Appendage expression driven by the Hoxd global control region is an ancient gnathostome feature," will be published online the week of July 11 by the Proceedings of the National Academy of Sciences.

Provided by University of Chicago Medical Center

4.6 /5 (18 votes)

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User comments : 35

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racchole
2.4 / 5 (5) Jul 11, 2011
COOL
Mayday
1.5 / 5 (14) Jul 11, 2011
Okay, okay, the line has played out. I guess it has fallen to me to set the hook.
Here goes: Intelligent Design?
whoyagonacal
4.3 / 5 (11) Jul 11, 2011
Aw c'mon, the trolls are going to show up in any case; no sense in encouraging them.
gwrede
1.6 / 5 (7) Jul 11, 2011
Heck yeah, ID. Whenever stuff goes beyond somebody's grasp.
Isaacsname
4.6 / 5 (9) Jul 11, 2011
In before neutron repulsion
BaconBits
4.7 / 5 (13) Jul 11, 2011
Isn't the way to think about this that the fish came first, i.e. these gene switches regulated the gene expression of the skeletal/limb structure of fins and as mutations built up in these and later gene patterns emerged they were extended and emplyed for more complicated limb gene expression but that ultimately their core function remains mostly conserved over 400 million years and highly diverged fish and mammal species use the same genetic mechanism to perform similar functions. No ID in this at all, just an effective gene pattern that began working well for its host 400M years ago and still does in its decendents today.

And look at all the cool things natural selection has selected for over that period of time using that same toolkit.
komone
3.2 / 5 (5) Jul 11, 2011
Hi Mayday, yes of course, (insert your preferred god) must have put it there, and that explains it. If you are the curious type, like, say, a scientist, you may then wonder about further explanation. What was exactly was the mechanism that (insert your preferred god) defined to place this apparent anomaly inside fish. What state of the world and what rules would be necessary for this to emerge. You may find that the answer is very like some kind of evolutionary pressure. Then of course, since (insert your preferred god) defined that mechanism, the story is over, unless you are curious and ask, what exactly would be necessary for such a state and such rules to emerge.... and so it goes on.
xznofile
3.3 / 5 (3) Jul 11, 2011
so which came first: the switch or the gene? my bet is that it controls a process that eventually developed into legs.
aroc91
2.3 / 5 (3) Jul 11, 2011
Isn't the way to think about this that the fish came first, i.e. these gene switches regulated the gene expression of the skeletal/limb structure of fins and as mutations built up in these and later gene patterns emerged they were extended and emplyed for more complicated limb gene expression but that ultimately their core function remains mostly conserved over 400 million years and highly diverged fish and mammal species use the same genetic mechanism to perform similar functions. No ID in this at all, just an effective gene pattern that began working well for its host 400M years ago and still does in its decendents today.

And look at all the cool things natural selection has selected for over that period of time using that same toolkit.


Exactly.
TheGhostofOtto1923
3 / 5 (6) Jul 11, 2011
The question is, why would god put fish genes in rodents? Isn't every species supposed to be de novo in noahs world?
Telekinetic
1.9 / 5 (9) Jul 11, 2011
Pluripotent stem cells can become almost any type of cell, i.e., heart, muscle, eye, etc. I would expect that the basic building blocks of a living cell would be standardized and interchangeable between species, but that the differentiation of species lies in the area of chromosomal type and in fertilization, where particular sets of DNA recognize only their counterpart, although even there, there have been exceptions of cross breeding in animals that are closely related. Let's face it, our earliest cousins had gills, which I wouldn't mind having now.
epsi00
3 / 5 (2) Jul 11, 2011
So the fish (could have ) walked before us!
Sinister1811
1 / 5 (9) Jul 11, 2011
This might increase the probability of finding terrestrial (as well as aquatic) life on other planets.

This would also mean that it's possible re-engineer extinct species.
FroShow
3.7 / 5 (3) Jul 11, 2011
@komone; by your post it doesn't seem to me that you've realized Mayday was trying to push buttons. In this case, ya, he trolled. But I gotta say I got a chuckle out of how he brought up an obviously controversial idea (for a physics blog).

@Sinister1811; Check out the TED talk by Jack Horner: "Building a dinosaur from a chicken": http://www.ted.co...ken.html

To me, it seems plausible that before fish there were species that moved about on the sea bed. Mobility on the sea bed would be an easier adaptation than mobility while floating in the water. Several mutations down the road, and ta-da: now life can swim and not have to cling to the 'wall'. But Life (the true intelligent designer) doesn't throw away useful code, so it keeps it in the DNA pool (maybe it's just lazy). Millennia later, when 'above the surface' is hospitable enough for Life, this old code is reactivated.

Just a theory, but plausible enough not to be stated.
yep
1 / 5 (9) Jul 12, 2011
Cosmic Serpent:DNA and the Origins of Knowledge by Jeremy Narby
Deesky
4.2 / 5 (5) Jul 12, 2011
This might increase the probability of finding terrestrial (as well as aquatic) life on other planets.

Why?
Sinister1811
1.2 / 5 (13) Jul 12, 2011
@Froshow - That's interesting. Scientists have already said that it's possible. I think if they could compare the genes of various birds, and work out which genes they all have in common, they could reproduce the ancient ancestor of today's birds. They could do this with other animals as well, I think.
Sinister1811
1 / 5 (10) Jul 12, 2011
This might increase the probability of finding terrestrial (as well as aquatic) life on other planets.

Why?


Why not? If the genes for limbs exist in fish, they might go back even further to say bacteria. It'd be interesting if they found the same genes in single-celled organisms.
Deesky
4.3 / 5 (9) Jul 12, 2011
Why not? If the genes for limbs exist in fish, they might go back even further to say bacteria.

That's a stretch - why would bacteria need limbs? Certain genetic sequences may have been co-opted later in time when multicellular organisms evolved, but you're not going to get a one-to-one mapping. In any case, what does that have anything to do with life evolving elsewhere in the universe, which was the basis of my query.
lovenugget
2 / 5 (2) Jul 12, 2011
i laugh at the ID drones.

also, mudskippers are an interesting example of a fish that uses their limbs to move across dry land.
TheGhostofOtto1923
3.3 / 5 (3) Jul 12, 2011
i laugh at the ID drones.

also, mudskippers are an interesting example of a fish that uses their limbs to move across dry land.
And humans are an interesting example of an animal that uses their limbs to move through the water.
http://en.wikiped...pothesis
frajo
4.5 / 5 (2) Jul 14, 2011
Similarity of two switches does not necessarily imply similarity of the switched entities. The relation between switches and switched entities could be an n:m relation.
LVT
3.4 / 5 (5) Jul 16, 2011
The question is, why would god put fish genes in rodents? Isn't every species supposed to be de novo in noahs world?


ID stands for ignorant design. God's not a very competent designer.
cyberCMDR
3.3 / 5 (3) Jul 17, 2011
When I read about this, I can't help but think of the ID trial where one of the lawyers supporting evolution wore a mousetrap as a tie clip. The mousetrap obviously had an original purpose, but was re-purposed for the function of keeping the tie straight. These fish genes may work with mouse genes in programming limb development, but that does not prove that was their original purpose. Same transmitter (control genes) but with a newer (upgraded?) receiver, which maintained similar control feedback mechanisms.
Sinister1811
1.1 / 5 (14) Jul 17, 2011
That's a stretch - why would bacteria need limbs?


To move. Certain bacteria have flagella, which helps them to move about. I don't know whether you'd classify that as like a primitive type of limb, or not but they certainly don't teleport.
Hoodoo
3.5 / 5 (4) Jul 17, 2011
This gets me thinking about panspermia, not IntDesign.
Why would bacteria need limbs? Well they wouldn't. But if those hardy bacteria were taking a comet ride to the next star system, a few tricks up their sleeve (so to speak) regarding limb generation could come in handy in future iterations a long way down the track.
IscopeU
not rated yet Jul 17, 2011
This doesn't make sense to me, but let me try. Basically what this article says is that the way limbs evolved, gradually, as the fossils show, is done by a mechanism found in this 'switch'.
Sound awesome, but they couldn't find it in an earlier experiment, now they can? Hows that...

How did this... "Maybe the key was expressing a gene earlier or later or in a specific territory, but it was just a modification of a program that was already encoded in the genomes of fish almost half a billion years ago and remains there to this day." .... "just a modification" came about in this experiment?
breadhead
1 / 5 (5) Jul 17, 2011
http://www.mathem...s__.html

You believe then, that the bacteria originally came to life by some accident, and did so with information to make limbs?
You have greater faith than I do.
Sinister1811
1.3 / 5 (15) Jul 17, 2011
I gather you have a more brilliant argument Froshow? Or do you disagree with the fact that certain bacteria use flagella to help propel their movement?
FroShow
3 / 5 (2) Jul 18, 2011
@Sinister1811; I'm curious why you would ask me.
No one could disagree with
the fact that certain bacteria use flagella to help propel their movement.
I'd like to point out though that flagellum are an extension to single cell organisms, whereas limbs are a property of multicellular organisms; they're quite different.
BUT, a stretch of the imagination: it's possible that flagellum-like appendages could branch multiple cells, allowing for relative motion between them, thus being the start of 'limb' like structures.
I don't know whether you'd classify [flagellum] like a primitive type of limb
-Sinister1811
Sinister1811
1.2 / 5 (14) Jul 18, 2011
Ok, thanks for that. I was just wondering why you rated my comment so low. But anyways, you're right - Flagellum and and limbs are two completely different things. So I suppose I deserved it. I slipped up earlier when I stated that the genes might also be found in single-celled organisms. And for that, I apologize to those certain people who pointed that out.
FroShow
2.3 / 5 (3) Jul 18, 2011
Aside: I hate the rating system all of these forums have; you can't rate separate ideas within a single post, you can't distinguish between what you like/agree with/find relative/humorous/offensive/etc.. with a single 1-5 rating.
... which is partly why it's so easy to be offended by what people type (it's hard to remove emotion from text, we all automatically impose a 'tone' to text in order for us to interpret it).
Ethelred
2.9 / 5 (7) Jul 18, 2011
You believe then, that the bacteria originally came to life by some accident
No. And yes. Bacteria originally evolved from something that wasn't bacteria. And all mutations are at least partially an accident. However Natural Selection is what shapes the organisms over succeeding generations.

and did so with information to make limbs?
No. Bacteria don't have limbs and can't as they are single celled organisms. Limbs didn't evolve till there were multicellular organisms.

You have greater faith than I do.
I have evidence that I go on. You have faith despite the evidence. Faith when you might be right is a virtue. Faith when you are clearly wrong is just being pig headed.

The reality is that the theory of evolution is NOT a proven fact of science.
Yes it is. At least as much as gravity.>>
Ethelred
3.2 / 5 (6) Jul 18, 2011
It requires the conversion of life from non-life.
Lie. Evolution is not about how life got started it is about how life changes AFTER it started. Lying about that won't make the clear evidence of change over billions of years go away.

onversion has never been proven to be possible.
Nor proved impossible. However there is every reason to believe that it is possible.

Even the simplest life on earth, which does not require a host, is far too complex to form by a series of accidents.
True. However the simplest life is clearly vastly more complex than the earliest life. And only Creationist keep lying about it being an accident. Mutations are accidents but Natural Selection is not.

first life was a form of life which does not exist on this earth any more.
And only someone that has already told several lies would ever claim that such life should be able survive with all the more life having it for breakfast.>>
Ethelred
3 / 5 (6) Jul 18, 2011
New genetic information, including at least one new gene, has never been observed in nature,
Purest ignorance or an utter lie. I don't know which but was just a few months ago that an article here showed a case of a modified copy of a gene in a species that still had the original and the two genes were doing different jobs. That is an increase in information.

I think that is enough of that aggressively ignorant anti-scientist. I have ripped that crap to shreds befoe.

Faith based on ignorance isn't admirable. Faith based on accepting a of pack lies supporting that ignorance is a bad thing.

Ethelred

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