Wings, Legs, and Fins: How Do New Organs Arise in Evolution

[00:00:00] SPEAKER 1:
It is my pleasure at this moment to introduce Professor David Wake.

(applause)

[00:00:12] PROFESSOR DAVID WAKE:
It’s my privilege to introduce the Hitchcock Lecturer today. Uh, as you see from your program, the Hitchcock Lecturer is one of the highest honors that the Berkeley campus can bestow, and, uh, we’ve had a very distinguished set of speakers. Our speaker today fits very well in, in that company.

I first met Neil Shubin when he was a graduate student at Harvard, preparing for what would be his major work on the transition from water to land in vertebrates. Uh, he was studying at that time with Farish Jenkins and with Pere Alberch and was preparing a large, essentially monograph-length, uh, review of limb development in amphibians. This, uh, this paper, which was published with, uh, Pere Alberch, uh, became a very influential piece of work and brought Neil to the attention of people in a number of fields beyond paleontology.

So, for example, comparative anatomists, uh, developmental biologists, people interested in the then very new field of evo-devo took note of this work. And Neil has continued on this pathway of integration since that time. He’s, uh, well-trained in fields such as geology and paleontology, where he’s probably best known.

But he also has done a lot of, and continues to do a lot of work in developmental biology, in particular in that subfield known as evo-devo. Uh, in addition, he is a comparative anatomist, a naturalist. He’s been in the field with me collecting salamanders more than one occasion, and, uh, is a person who’s at, at home both in laboratory and field work.

So I, I really think that as an integrative biologist myself, that Neil Shubin exemplifies what we mean by integrative biology. Neil came to Berkeley as a Miller Postdoctoral Fellow, and that’s where our interaction began. And, uh, I must say that a most pleasant fifteen-year period of collaboration started at that point, and, uh, we became good friends and, and I became a great admirer of him and his work ethic and the way he goes about thinking about problems, the way he sees problems, and the way he’s able to convey his enthusiasm for his work to others.

Uh, following a– this successful Miller period, he went to the University of Pennsylvania, where he started his career, uh, on a very fast track because he gained rapid attention by his outstanding discoveries in the fossil field and also by his continued work in evo-devo. In 2000, he worked– he moved to the University of Chicago, where he is now the Robert Bensley Professor of Organismic and, uh, biology and anatomy.

And it’s a great pleasure to introduce you today, introduce, uh, you today to Neil Shubin, who will speak on wings, legs, and fins: How do new organs arise in evolution? Welcome.

(applause)

[00:03:28] NEIL SHUBIN:
Thank you. It’s, um, thanks again to the Hitchcock, uh, Lecture Committee for making this, uh, possible, my return visit to, uh, to Berkeley. And, uh, it’s a decided pleasure to be introduced by my mentor and friend of, uh, over eighteen years, uh, David Wake.

The underlying theme of my, uh, two lectures is really that some of the ma– most of the major questions, important questions in biology are solved by an integrative approach that unites fields from diverse disciplines. That what defines us are our questions, and that the tools we use can span multiple fields. And this is nowhere more true in evolutionary biology, in particular in those parts of evolutionary biology where we’re trying to reconstruct and understand evolutionary history.

Now, in stepping back a bit, really when we think about this being the Darwin Year, um, two great concepts really stem from The Origin of Species with Charles Darwin. I mean, the first is obviously natural selection, that there’s a struggle for existence, uh, that brings about a change in populations over time. The other, and the one that really has captured my imagination, is the notion of descent with modification.

That is just like we are modified descendants of our parents, and understanding that descent with modification in our own family enables us to see our family trees, that that our family tree extends to other species, and our own species is a modified descendant of other species that had existed in the distant past. And that through this process of descent with modification, the very simple beginnings can produce an extraordinary evolutionary tree. And it’s really that’s what I’m going to focus on today.

Yesterday, the take-home message was, as if those of you who were awake for the last slide, saw that the, um, that evolutionary trees are very important, that we can make very strong predictions about where to find fossils that answer major gaps in our knowledge of evolution, and that the way we can best interpret them is not as a linear series of events, uh, a ladder-like process, but really as understanding them as a branching tree of diversity and adaptive di- diversification and radiation. And so to understand that, we, we really kind of looked at the level of, of whole animals yesterday. Today we’re gonna take a sort of bore in a bit and look at organs.

How do new organs arise, uh, through change, through time? When you look at organs with the principle of descent, with modification, it really becomes very clear that to understand the new in evolution, you have to understand the old. Because of- often what we have to do is trace organs through time to understand what the same organ is in different species over time.

To understand the sequence of changes that happen in an organ in dif- from one species to the next, we have to have a way of defining what the same is. What’s sameness? What’s the same organ in two different creatures.

So to understand novelty or new organs over time, we really have to understand the old, and that means understanding what is the same structure in different kinds of creatures. Now, at first glance, you could not imagine a subject more boring or esoteric than trying to come to grips with what’s the same, uh, in evolution. But I’m going to tell you that it’s actually arguably one of the most important, uh, concepts in all of biology, and so much of what we do as comparative biologists, evolutionary biologists, and even people interested in biomedical discovery, uh, stems from that.

And where to begin, we begin with noses. So here is, um, a famous nose. Uh, this is, uh, Basil Rathbone

(laughter)

from Sherlock Holmes. And the question really is, you know, what is a, what is a nose? What is a nose in different species? Is it the same as a nose in some other kind of creature, like this creature here with this object, um, uh,

(laughter)

perched on the end of it?

(laughter)

Is it the same as this, uh, proboscis at the end of of this creature? Is this the same organ in these different species? Is it the same as a, a bill of a bird, of the giant proboscis of of a paddlefish, or the many different kinds of proboscises we find, uh, in arthropods and other creatures?

Are these the same structures? How do we know it? What does it mean in biology to be the same?

This is the starting point for understand- for understanding how new features arise over time. Now, you can say, “Wow, that’s really kind of esoteric.” Thanks for getting into that.

But I will tell you that it’s arguably one of the most important concepts in biology, as I said before, and so much of what about– that exists of why it’s important, we take for granted as biomedical researchers. Look at the title of this paper, Animal Models of Human Disease: Zebrafish Swim into View. Zebrafish and their development are a model for human blood formation and formation of the pancreas, and diabetes models, and so forth.

It’s a model for biomedical discovery. Why stop at fish? A Drosophila model for Parkinson’s disease.

The only way that understanding that is really understanding that what the events we’re seeing in Drosophila are the same, uh, in this, uh, flying insect, uh, and humans. Indeed, if you ever need an example of why our con- evolutionary connections to the rest of life on this planet are, are important, I encourage you to go on a we-website, and that website is the Nobel Prize in Medicine. And what you see here is a list of the Nobel Prizes, uh, in Medicine over the last few years.

Who have they gone to? They’ve gone to people looking at Drosophila, fruit fly, to understand the genes that, uh, many of the genes that control development. Two Nobel Prizes in the last several years have gone to people working on a little tiny worm the size of a comma on the piece of, on a piece of paper.

Yet that little worm, Caenorhabditis elegans, is telling us how, you know, cells die, patterns of cell programmed cell death, or how our genes are silenced. And indeed, it’s discoveries such as that which have important ramifications to drug design and human health. Understanding the cell cycle has, has been, has de-de-dependent on studies of creatures as bizarre as sea urchins and yeast.

And why stop there? Memory, um, and, and sea slugs, although they’re not this particular one. And of course, since we have this individual on the page here, we also learn about ourselves through, uh, corn.

So the, um, so the important thing here is by applying, understanding basic biological, um, discovery and applying it to humans, we really have to have an understanding of what the same is in different creatures. Now, like all important concepts, this concept has deep, deep historical roots. Natural philosophers, indeed philosophers, uh, for centuries have been thinking very hard about this question.

And one of the more prominent players in this regard, uh, is Sir Richard Owen, shown here. Um, shown here. Shown here.

Oh, there we go. Oops, there we go. Shown here.

Uh, this is Richard Owen, he’s on your left. And Owen was a, uh,

(laughter)

Owen was, uh, an anatomist, uh, uh, you know, in the mid 1800s, and it was a wonderful time to be an anatomist because you could truly be a, a comparative anatomist. I mean, he was fortunate to be an anatomist at a time new creatures were being discovered, whole new kinds. He named Dinosauria.

Uh, he, you know, he originally described the skeleton of a gorilla and so forth. He was uncovering great natural diversity, and in uncovering na- great natural diversity of different kinds of creatures and their skeletons and so forth, he saw common plans, common designs. And this, when I was a graduate student, um, this book, On the Nature of Limbs: A Discourse, by Sir Richard Owen, uh, really caught my imagination in a very big way because it’s in this book where he lays out, in a series of figures, his notion of sameness.

And he had a couple different notions here, and it’s worth spending a little time on them ’cause we’re gonna touch back to them as we get into some experimental work that’s been happening in my lab lately. This p- this figure, it’s a beautiful figure. It’s actually, you fold it out.

It’s, like, yay big, uh, in the volume. And he shows a human skeleton here, and he defines several different kinds of sameness. And right off the bat, he’s laid off the human skeleton with birds and other creatures, and you could see he’s colored it in to make specific comparisons of the same cre– the same feature in different, in different creatures.

You know, the vertebrae, uh, the appendages, and so forth. And this whole treatise was really about limbs. And he s– he sort of argued, like many natural philosophers at the time, for two different kinds of sameness.

One is similar features in different creatures, and the other is similar features in the same creature, like arms and legs. They have a similar sort of, uh, plan. And, you know, the basic take-home message is if you look at the arm of a human, the wing of a bird, and, uh, or the limb– any– of any limbed animal, and you look at the skeleton inside of it, there’s a common structural sort of theme or design, which we have one bone going to two bones, going to a series of small bones, the wrist or ankle bones, and then the digits.

You see that both in the leg and the arm, and you see it in different species. This, this frog arm here actually has two bones, but they’ve been fused up. But so the changes we see are due to changes in the size and shape and sometimes loss of individual bones.

Now, the sameness that Richard Owen talked about here is between these appendages is very different from from that we see, say, a fly wing. That this is somehow a different structure. It’s not the same, even though it’s a wing, just like a bird wing, but it’s composed of different bones.

It’s essentially a different, uh, different design. Now, Owen was not an evolutionary biologist, and so just like I’m dancing around the word history and evolution and so forth, Owen spent this whole book, On the Nature of Limbs, dancing around that concept as well. Now, this whole notion was actually a hot topic for a long time.

Uh, these– this, this pattern of similarity was identified by people beginning in the 1600s, Vicq-d’Azyr. One of the, um, key players here, uh, was, uh, preceded Darwin by several centuries, and this is a Saint-Hilaire. Saint-Hilaire was a natural philosopher from France, and he looked at this same pattern actually several decades, uh, before Owen, and he came up with a really wonderful law, a natural law, uh, called the law of connections.

And he, uh, he was big in the laws, as a lot of his, um, contemporaries were, to try to understand what are the regularities behind the designs of bodies. And his law of connections was basically that the way bones articu- the pattern that bones articulate with one another is highly conserved among different creatures. That’s the, that’s the way you can define sameness.

And so he identified this one bone, two bone, little bone fingers, um, design as a pattern of connections that’s essentially invariant, okay? And that that is the, um, that that’s the design principle. And he extended this throughout the body from the ears and the ear ossicles, and the ribs, and the vertebrae, and so forth.

Everything changed. Saint-Hilaire, Owen’s ideas, everything changed with Charles Darwin, obviously. And Charles Darwin saw this pattern as well, and, you know, he has this famous quote from The Origin of Species, “What can be more curious than the hand of a man, formed for grasping, that of a mole for digging, the leg of a horse, the paddle of the porpoise, and the wing of the bat should all be constructed on the same pattern?”

And what struck Darwin was that despite significant, um, variation, despite significant variation in function, right? So you have wings, you have flippers, you have sort of generalized forelimbs of different kinds, the forelimbs for digging and, uh, running and so forth, that this one bone, two bone pattern is sort of the template for all this adaptation. And it, it became clear to him that, you know, the functional argument for why you have this one bone, two bone, little bone ray pattern is m- useless.

It really only makes sense if these creatures evolved from a common ancestor that also had this, this, this one bone, two bone, little bone ray plan as well. So he explained this, this concept that Owen was d- of sameness, that Owen was dancing around for years, and Saint-Hilaire was trying to develop laws of form for, he explained it, uh, through the principle of descent with modification. And this concept is really powerful because what it does is it enables us to make predictions.

That we could then say that if, you know, if, if this pattern, one bone, two bone, and so forth, um, has a history, we should see that history in the rocks. We should see that history in comparative anatomy. It should be written in the bodies of other animals.

And that’s exactly what Darwin did, and he said, you know, w-w– I mean, he implied that essentially you would see that this pattern in other creatures that don’t have limbs, what about the fins of fish? I’m just showing you a, a forelimb of a coelacanth here. And indeed, when you layer it in, um, you see Uh, you see the skeleton, and again, it has the one bone, but only it doesn’t have the rest of the, the pattern as well.

You should see some, but not all of that pattern as you go deeper in the evolutionary tree, uh, if you will. And it’s those predictions I’ve spent my time as a paleontologist trying to, to look at, to see the assembly of this pattern, the one bone, two bone pattern and so forth, by finding fossils, looking at genes and development, and so forth. And indeed, when you look at Devonian age, um, limbed animals, um, from about three hundred and sixty-five million years ago, this one’s backwards, sorry about that.

But you see the one bone, two bone, little bone finger program, um, already set up in the earliest limbed animals. And as we look at their finned relatives in the fossil record, things like Tiktaalik and the other creatures in the evolutionary tree, more distant and so forth, we begin to see the assembly of this pattern. Um, let me…

So here’s a, here’s an early limbed animal, and then you have the other creatures on the tree, uh, each one further away or more distantly related, uh, to this, these two limbed animals. Well, you see, an early limbed animal here. It has the one bone, two bone finger, uh, pattern.

Tiktaalik has one bone, two bones. Has other more distal bones, which we can actually compare in some ways to this cohort. And as you go deeper and deeper and deeper in the tree, what you still see is this one bone, two bone, little bone ray pattern already set up in fish fins, doing a diversity of things early in the radiation of these kinds of fish in fins with fin webbing.

And it turns out the fossils are very useful for us to understand and trace this pattern and its adaptive diversity, uh, in the Devonian. Things get less sure as we begin to look at extant or recent fish. So here you have a fin of a, of a lunged fish.

Here you have fins of paddlefish and sharks and so forth. And when you see, you have a cer– what appears to be a very big gap between extant limbs and extant fins. Although, as you get into lunged fish, no surprise, you start to have one bone at the base, just like all these other creatures, as opposed to many bones at the base, like other fish, more deeply, Deeply more distant in the tree.

So we can actually begin, as comparative anatomists and so forth, to begin to really understand what ha-happens to the same appendage in different creatures. And for better and to better and worse, and we can make some hypotheses about, you know, what is the same bone in different creatures. This one bone is the same bone in all these different creatures.

And then it gets a little tenuous as we go further out in the, in the fin. But we can still do this to different degrees of accuracy using different kinds of fossils. Now, when we talk about sameness, I sort of want to introduce a concept, and I- and I’m left with some no real analogies, and so I just sort of made one up when I, uh, um, on the way and when I was thinking about this.

And when you think about, you know, an organ, an organ has parts, and then an organ also has processes that make those parts. So you can think about the same thing at many different sort of hierarchical levels so that, you know, you can think about the model, this sort of obnoxious car here, the, the, uh, Hummer, right? And you can trace the history of the, the car, the Hummer, over time from, you know, small sort of obnoxious car to big obnoxious car to sort of smaller recession time, uh, obnoxious car.

And then you can disassemble it into its pieces, its parts, which also have a history. The tires have a history, uh, of, of, of processes that are behind them. The windshield, uh, the, the lights, the windshield wipers, and so forth all have histories.

So you can think of the, the sameness and the history of the whole entity, the car, the Hummer in this case, and you can think of the sameness and the history of the parts that make it up as well. But you can also think of the history of the processes that make these parts, the, the vulcanization, the processes behind the making of the rubber, and the steel, and so forth. So you can think about this at many different levels, and each level has explanatory power.

Indeed, the, a, a, a Hummer and a Prius appear to have very little in common, yet at the level of the, um, of the, the processes that make the car, that, the tires and so forth, they share quite a bit. And so, um, essentially, I wanna look at organs in that way. I don’t wanna push the analogy too far ’cause like all analogies, it’s, it’s limited.

But when you think about a limb with a skeleton inside, you can ask about the limb and the, the, the history and the, the sameness inside this organ, the pattern of bones here, Saint-Hilaire and, and Owen and, and, uh, and Darwin’s pattern. You can ask about its parts, the bone and the cartilage, and then you can also, on top of that, ask about the sameness and the history of the, um, of the toolkit, of the biological recipe and processes that build, uh, these structures in different creatures. And it’s really kind of linking these, these different levels that we’re going to spend our time today on in the, in the talk.

So what I want to do is spend some time on this toolkit issue, and, um, to do that, we’re really gonna focus a little bit on limb development and how it arises. You know, you think about development, it’s one of the most wonderful problems in all of biology. You begin as a single-celled egg.

You end up as a two trillion cell adult. Well, a nine trillion cell adult, only two trillion of them are yours. The other seven trillion are, uh, are, um, are microbes that inhabit you.

Um, but you know, over time, that one cell becomes a very precisely packed organism with the cells packed in the right way, differentiated cells doing their jobs in different ways. And much of this, this, this development is written inside the DNA that exists within the, uh, within the egg and its interaction with the environment around it, as well as the internal environment, uh, in the, in the embryo. One of the outcomes of that is actually, we can watch development happen as things get bigger, and they get more complicated and differentiated over time, and the limb is no different.

Uh, so limbs begin as little pouches out the side of the body. And over time they grow out. And as they grow out and extend out of the body, it’s called a limb bud at this stage because it’s a limb.

And it’s a bud, and it comes out of the body. And inside the limb bud, cells go from kind of looking all alike to differentiating. You start to see cartilage cells and eventually muscle cells and, and the cartilage differentiate– develops into bone and all this good stuff.

And you can watch over time the formation of the pattern as the, um, as the, uh, uh, the limb bud grows out. Now, underneath this, controlling this in many ways, are a series of events that are sort of written in the genes, if you will. And Here I have a limb bud, showing you some of the main signaling centers that if you were to open a textbook in, in, in, uh, developmental biology or actually introductory biology that you’d see.

And this is a limb bud with two patches of tissue that are known as signaling centers more or less. And what they do is their behavior actually promotes and patterns the limb in many ways. Now, there are factors that exist in the body that actually set these things up initially early in development, but then once they’re set up, they’re really major properties of how the appendage grows and forms in early development.

And one thing that underlies it is a series of genes that are turned on, and we can actually map those with a variety of techniques to see their activity and look to see the chain of events by which this, um, these, uh, two patches, the AER up here and the ZPA here, I’m just gonna use their, um, uh, their, their– the, the abbreviations to talk about them, and then there’s a series of genes that interact. So in the ZPA, there’s a, a, a prominent gene that marks ZPA activity called Sonic Hedgehog, here shown as SHH, and in the AER, there are genes known as FGFs, okay? Namely, FGF8 is a real prominent one.

And let me just go into these and, and just talk a little bit about them because they’re going to be our roadmap to look at sameness, uh, in, in a variety of different limbed and non-limbed animals. So let’s go back one. So…

Oops. So if you look at an embryo, here’s an embryo early in development. This is a chick embryo, and it’s stained with one of these, quote, dyes, if you will.

And what it does, this is attached to FGF8. So it’s a marker for the AER. Okay?

And you could look at the AER here, and it’s where this gene FGF8 is, is, is turned on. It’s turned on nowhere else in the fin bud, and it’s a signature of that. And when you pop this thing under a microscope, what you see is it has a ridge there.

It’s a ridge of tissue. And you see, if you were to cut this as a section, this is what that section would look like. And it’s a thickened ridge of, sort of, epithelial-type cells, uh, separated from sort of more disorganized cells in the center.

And it has special properties. And those properties are really important for our story, because it when it has a property such that it seems to promote the growth of the appendage. So that if you remove the AER early in development, say it’s stage eighteen here, you’re left with the limb with only a humerus.

If you remove the AER at a slightly later stage, say it’s stage twenty, um, you’re left with a, uh, a limb that has a humerus and part of a radius and an ulna. And so you’re left with more the later the stage you remove the AER. It clearly promotes the growth of the appendage in a lot of ways.

And so that’s a stage-specific effect. So the AER is very important in that regard. There’s another one, and that’s, um, the ZPA.

Remember we talked about the ZPA, and it had that gene sonic hedgehog, the SHH gene. This is, uh, another chick embryo, and what you can see here is here’s a sonic hedgehog. It’s been stained there.

It’s also been stained with FGF8. So you see the AER here, and there’s the ZPA. Now, the ZPA seems to be involved with a lot of events across the body.

In the appendage, it has– it also has a lot of events that are associated with it. But one of the real prominent effects with the ZPA and sonic hedgehog lies in the, um, differentiation of the digits, the fingers. Because if you look, what you can do is you can take this ZPA t-tissue, you can dissect it out, and you can pop it on the other side of the appendage.

When you do that, you get a very characteristic effect, and you can also get the same effect when you cause Sonic hedgehog, the gene that is turned on here, to be expressed on the opposite side ectopically, um, misexpressed on the other side. So you can do all this surgically, or you can actually implant a bead of a compound known as retinoic acid, a form of vitamin A, which will induce another patch of sonic hedgehog activity. So normal would only have sonic hedgehog in the ZPA, which is the normal ZPA here.

But you can re– induce another ZPA, um, an ectopic one through this bead of retinoic acid, and voila, what you get, you get a mirror imble– image duplication of the, of the fingers. Okay, and in a variety of different species. And if you knock down, if you sort of inhibit a Sonic Hedgehog expression or take out the ZPA in some ways, you reduce the number of fingers.

So it seems to be the, the, um, specification of the fingers as you go from the pinky to, uh, the pinky to the thumb side, it really depends on the activity of the ZPA. So we really have these two centers, the AER and the ZPA. This is a good part of the toolkit that builds appendages.

Now why am I going into all this? Um, good question. Um, well, it’s a useful question to ask given light of our Hummer analogy I showed you earlier, and that is the notion that, well, what’s the sameness of the toolkit?

We can trace the bones. What about the toolkit itself? So the idea to here– what we have to do here is to look at the toolkit, the AER and the ZPA, and ask the question, what are they doing in fins?

And if we choose our creatures right, we could begin to come to get some, and these are the fins of these creatures, and we do it along a, a, a phylogenetic evolutionary tree mapping with Chondrichthyans here, sharks, skates, and rays. Actinopterygians, which are ray-finned fish like paddlefish and, and Teleosts and so forth. And look at limbed animals.

We could begin to ask the question is, how ancient is the toolkit? Is it the same thing in fins and limbs? Is it doing similar kinds of things?

Are genes doing the similar kinds of things? And this is another way of asking how these organs, uh, came about. So what we’ve been doing in my lab is looking at fish, and most lately we’ve been doing, doing looking at sharks, not great whites.

But we’ve been looking at skates, uh, ratfish, the three major groups: skates, ratfish, and sharks. Uh, it’s a challenge working with some of these creatures. It’s not like you can buy shark embryos at the store.

Um, what we get them from is, uh, the Shedd Aquarium in Chicago. Uh, we also get them from the Marine Biological Laboratories in Woods Hole. But provide us a supply of about twenty or thirty eggs a month.

Not a whole lot to do, uh, embryology on, but enough for our purposes. This all began really in my laboratory, um, with a postdoc by the name of Randy Dahn. Randy worked on chicken eggs for his PhD, looking at limb development.

And when he looked at shark eggs, he saw that they looked a lot like chickens, so he decided to do all the experiments he did on chickens, only in sharks and skates. So this is a wonderful comparative test to see how they lie together. One of the things you’ll see is every time I show a molecular biologist from my lab, uh, in this talk, they’re in the field collecting fossils.

So I want you to know that molecular biologists make very good fossil finders, so there’s, there’s hope for those of you, you guys yet. All right, sorry about that. Anyway, so, um, you can ask the question, is there, there’s AER in limbs?

Here it is. And you can see the section here, and here’s the, um, here’s the FGF8 expression. You look in shark fins, and what you see is, in a skate in this case, Chondrichthyan, there’s the FGF8 expression, and you also have, uh, an AER.

And in fact, you have an AER, and it actually gets long and, and trans– and, and turns into another structure called the AEF, which is related, uh, to fin formation. So it has the AER, and that seems– and it’s also in all fish fins. And so what you have is we can trace this as the same structure all the way through.

Now, what about the ZPA? ’cause you remember the ZPA has this sonic hedgehog expression here, and when we misexpress it With retinoic acid, we get these duplicated structures. So for this, um, we look at the, the eggs of these things.

And so here you see the yolk of a skate, and there’s the embryo on top of the yolk, and they, they develop inside an egg case. Uh, here’s a shark, uh, with again, with the embryo, and you can treat these things by injecting, um, retinoic acid, and this took a while to figure out, of different concentrations into the egg at different stages, and to see what it does because this, in the, in this chick, what it’ll do is induce that ectopic AER with the sonic expression, and you’ll get duplicated digits. In, um, in sharks, here’s the normal where you have, uh, the, uh, expression of the, of sonic hedgehog in the, uh, posterior margin of the fin, just like in a limb.

So the expression, the activity of the gene is the same. And then when you treat it with this retinoic acid, you turn it on, you turn it on all the way distally, and then you also turn it on on the anterior end as well. So you get a, a–

You induce, uh, expression in, in novel places, particularly in the anterior end. You can ask what the m-, the anatomical readout of all this is. Here’s a dorsal fin, and you can see a dorsal fin.

This is the normal one, untreated, and you can see it has… The cartilage is stained blue, and you can see it has, like, little, um, little stubs here. That’s the axis of the fin, and off of this come these rays.

When we treat it with retinoic acid, more often than not, we find, voila, a mirror image duplication. That is, you end up with an axis here, an axis here, and rays coming off of either side. And these axes can take– these mirror image duplications can take different forms.

But again, in chicks and in chondrichthyans, and in not showing you, but also in other kinds of fish, what do we find? We find a great continuity of portions, of big portions of the toolkit that make fins and limbs, AER, ZPA, and I’m not even showing you all the other genes in that cascade that are involved, uh, in this formation. So the beautiful thing here is when we find it in a lot of these groups here, we can begin to say that this genetic toolkit is the same thing in all these creatures, and we can begin to say that it was a property of the common ancestor of all fish with appendages.

Now, how do you begin to approach the question of comparing this to creatures that don’t have appendages at all? So appendages had to come in being, come into being at some point in, in evolutionary history. And for this, what we begin to use is one of Owen’s notions, that is, to look at the repeated parts in the body.

And this is Vesalius showing the human skeleton, and what you see here is a hind limb and a forelimb. And you can see there’s lots of repeated parts in the body. There’s repeated vertebrae, there’s repeated ribs, there’s repeated appendages between forelimb and hind limb.

Lots of repeated parts in the, in the body. To Owen, this was really significant because what he did, even though he wasn’t an evolutionary biologist, what he did was he showed he had an idea that all this diversity that we see here in these bodies with all these repeated parts can be traced with something he called an archetype, which was a phys– a philosophical ideal. Uh, this little thing here that does not exist in nature, okay?

But, um, to Owen, it was the sort of thing that all, uh, vertebrate animals’ diversity is derived from. It basically consisted of a series of repeated parts, of the vertebrae and the ribs and the, and so forth, and that the appendages and the jaws and the heads all come about from the consolidation of a, of the, the, um, the, uh, the, these repeated parts in different ways to make different appendages. This is a very attractive idea to comparative anatomists and actually to, uh, developmental biologists as well.

And let’s look, just take a peek at a fossil shark, and I’ll just show you how we have been approaching it. Now, here’s a shark, uh, known as Xenacanthus. It’s, uh, a fossil shark, and you can see the appendages here and the– and, and, uh, ribs and so forth.

And what really sort of caught a lot of people’s eye, and I’ll show you one of the people who was very important in this a little bit in a second, um, is this area here ’cause look at the repeated parts. Here is the gill cell skeleton. This is the j– upper and lower jaw, and then you have the gill structures, and you see they form these little hoops.

And doesn’t it seem… And this is the shoulder here and the fin. Doesn’t it seem like the shoulder is a repeated part of the gill, uh, of the gill structures, the structures that support the gill skeleton?

And this was a, um– The study of these gill arches has been very, very, very important in understanding anatomy. Because what you see is, let’s just look at the front end and these repeated structures. I’m not including the shoulder here.

What you have is several different gill arches. There’s the first arch, which is the jaw arch, which I’ve colored in here, which is the upper and lower jaws. There’s the second arch, which is the hyoid arch, which consists of this bone here and another bone.

This bone’s very important. It’s gonna appear later in the talk. So remember HM, hyomandibula.

And then you have a series of these arches, the gill arches, which support the gills. This really captured the imagination of comparative anatomists, and most of famous of these is Karl Gegenbaur, who is a sort of father of comparative anatomy in Germany. And he came up with a notion, um, that basically held, and this is the gill skeleton, this is the mandibular arch, this is that hyoid arch, and these are the gill arches here.

He basically said is if you compare the, these structures, the shoulder is the same thing as these gill arches, and the appendage skeleton, the fin, is the same thing as these rays in blue that extend from the gills. And he proposed this gill arch hypothesis that everybody laughed at. And it was basically the notion, he took it one step further.

He says, not only are these the same thing, but that fins arose as being modified gill arches. And it was just– It was a hypothesis that was almost, um, uh, quickly ignored after it, it’s, it, it appeared.

Um, and Andrew Gillis, uh, is a, a, um, a graduate student in my laboratory, and this is Andrew, again, in the field. He te- happens to be a very good fossil collector as well. And, uh, he decided to, to look at this question, to ask the question, Gegenbaur’s question.

The idea is, well, do the gill arches have the toolkit? Do they have the AER and the ZPA? If so, what does that mean, and how do we interpret it?

So this is what it looks like. There’s the gill skeleton shown in textbook view. This is the real world, so it’s a lot harder, uh, to see.

Um, but basically, what you have are the gill rays here. See these gill rays shown in, in, in, in red? These are the gill rays themselves.

So this is what Gegenbaur would compare as being thin, um, um, s- similar to the fins. And so the question is really, when we look at the structures that pattern this, do they have the AER and ZPA? Do they have the toolkit that makes, uh, appendages, aspects of the toolkit that make appendages?

And when you dissect it out, it looks like something like this. You have the, the gill cartilages and then the rays that extend from them. So let’s look at the AER.

Here’s a chick limb. Again, there’s the, uh, FGF at the tip, at the AER, and there’s what it looks like in section. Here’s the, uh, skate fin that Randy, I showed you from Randy’s work with the, with the fold.

And then when you look at the arches, what you see is we’ve removed the, uh, the gill arches here. So this is all damaged, so you have the stain in there. But here’s the strip right there.

And when you look at this strip, it’s stage-specific. So you’ll see the arches in the front in this particular preparation are lighting up with the FGF8. The ones in the back haven’t lit up yet.

But when you section them, what you find is a very similar histology at the tip, uh, as to the, the limb. Indeed, when you remove this AER, it’s the same stage-specific truncation of development. So the AER seems to be functioning in the same way with a similar set of genes, which I’m not showing you, I’m just showing you one, uh, in, in sharks, shark gills and shark appendages.

Again, to ask the ZPA, is that Sonic Express? So here’s Sonic Hedgehog, is it turned on in the posterior portion of the appendage? Here it is in the chicken.

Here it is in the skate. And when you look at the arches, what you see here is the f- the, the fin, and there’s the Sonic being– its activity turned on in the posterior portion.

And here it is in the arches, all limited to the posterior, the rear portion of each gill arch, right at the area where the gill rays will form. And then we looked at other things like the receptor for it and so forth. And so there’s other parts of this cascade.

I’m just sort of taking the top-level comparison here. The question then becomes is, let’s treat it like a limb. If you treat it with RA, do you get this other patch of sonic hedgehog turned on?

So you inject these things with retinoic acid using the Same treatments, and, uh, boom, what you see here is the normal with the, you shouldn’t be looking at side-on view of the arch, and here you see the he– Sonic Hedgehog. And then you see a stage-specific effect. This is a gill array that’s in the face, that’s induced another s– patch of expression in this particular arch on the other side.

Okay? And it’s stage-specific, so this one’s still showing it lightly. If I was to do it slightly later in development, this thing would go off, and you’d see it, uh, here in more, in, in deeper, uh, this deeper stain.

The question then becomes: what is the morph– the anatomical readout of this? And so you have the– it’s behaving in the same way. So here’s a chick limb.

Here’s one when you treat it with retinoic acid. Again, you induce another ZPA with sonic hedgehog expression. And, um, what you see is: here’s the normal, and then in the– uh, in the treated ones, you find rays branching out on the opposite side for all purposes, intents, intents and purposes, being a mirror image duplication.

And we can dissect these things out and characterize, uh, what these, uh, what these duplicated rays look like. And for all the world, it looks like they’re coming out from the opposite side of the, of the gill cartilage. And this gets even more exquisite as we look in more detail.

There’s a relationship between the AER and the, and the ZPA, between the genes in them, uh, the Sonic Hedgehog and FGF8. There’s all sorts of intermediary genes and a feedback loop between them, and that feedback loop and all those genes are present doing similar things in the, uh, in the, uh, gills and in the gill, gill rays and in the appendages. So it really seems, at a developmental level, that the toolkit that’s used to pattern an appendage, the fin in this case of a shark, is the same toolkit, is the same thing as is patterning the gill rays.

This is a, a developmental extension at the sort of level of the mechanisms that make anatomy, um, uh, of Gegenbaur’s, uh, Gegenbaur’s theory. The question really comes down to how would you know if it’s a, if gills actually were transformed into these things over time? And what we need here are fossils, and this is where fossils would tell us the sequence of stages and the transformation perhaps of gills to, to rays.

Right now what we know is if you look at jawless fish, which don’t have appendages but have these gill rays, okay, they have a full set of rays that are sure very large in the posterior end. They’re very, you know, very well-developed. Ideally, what we’d like to find is intermediate stages in this process in the fossil record, and all someone has to do is target Silurian Age rocks to look for it to test their hypothesis.

The other thing about these, uh, gill cartilages, um, is they’re wonderful for anatomy. Um, here you see the arches again. It’s the, you know, here’s the, the, the upper jaw and lower jaw, the first arch.

Here’s the hyoid arch with the hyomandibular there, and the gill cartilages. They all develop within these swellings, the branchial arches, that develop in the front end of the embryo. Here’s, uh, the pair of eyes, and you see there’s a pair of arches here that we colored in.

If you follow the fates of the cells that are in there, and these cells come from a variety of places, a-as well as develop in situ, these cells differentiate into respective structures in the arch. You can look at any creature that has a head, take a human, and you see these same branchial arches with this first pair, second pair, third pair, and so forth. What happens in a human with these arches?

They become portions of– the first arch becomes a portion of the lower bo– jaw and two bones of our middle ear. The second arch becomes a, a bone that supports the throat and one bone in the middle ear, and then the others become portions of the voice box. The take home message here is that developmentally, the, uh, the bones that you’re using, many of the bones and muscles and nerves that you’re using to hear me with right now, and many of the bones and muscles and nerves, or some of them, that I’m using to talk to you with right now, correspond to gill structures developmentally, uh, in fish.

Now, what’s interesting about this story, and this is– shows the importance of integrative biology and understanding descent with modification is, okay, you see this in development. But in paleontology, in the fossil record, what I should see is a transformation of a, uh, of, of jawbones into middle ear bones, and a transformation of a second arch bone, namely this hyomandibula, into, uh, into an ear bone. And guess what we see?

When we look at the fossil record in comparative anatomy, what we see is the hyomandibula, that hyoid man– that, that hyoid arch gill bone. Over time, it gets smaller and smaller and smaller. Such, such we’re in Tiktaalik, which I’m not showing here.

It’s intermediate in condition, and then it gradually shrinks to go into the ear to become the stapes. Fossils and embryos showing the same story. And what about those jawbones that go into the, uh, into the middle ear?

Same thing. If you look at the jaw of things we call reptiles, which have multiple bones in the jaws, you can trace two of these ones in the back. They get smaller and smaller and smaller till they translate into the, into the middle ear.

So development and, uh, fossils are showing us the same thing in the, in, in the ear. And it’s also showing us something very important about descent with modification because the same things in different creatures, with descent, if descent with modification is acting, the same thing doesn’t have to look like, look like it. That is, these middle ear bones, this stapes here, looks nothing like a hyomandibula of a shark, yet it’s the same thing in different creatures.

These two bones here, the malleus and incus, look nothing like the two bones in the back end of one of these jaws, yet it’s the same thing in an evolutionary sense. And that’s the power of descent with modification, because over time, with small changes, you can get great differences. And we can pick those differences up when we look at embryos and when we look at fossils.

So the take-home message to much of what I’ve been saying is that similar biological recipes make different organs, whether it’s gills, uh, rays, and appendages, um, and I’ll show you some other cases. But the important thing in terms of thinking about descent with modification at the level of recipes or toolkits or mechanisms that make, uh, bodies, is that new organs can come about by the modification of a-ancient recipes. Just like we have descent with modification, and we can interpret it at the level of anatomical structures, we can have descent with modification at the level of the toolkit, the processes, and the genes that compose that toolkit, uh, that make, uh, that make organs.

And so this allows us to return to Owen’s theme really, in the sense that, you know, he was saying basically that, you know, these appendages are not– are, are the same thing, but they’re utterly different from something like this, which is the wing of a fly. And indeed, when we look at Darwin, and we follow descent with modification, that appears to be correct in an evolutionary sense, is that fly wings have a separate evolutionary origin than do the appendages of vertebrate animals. But when we start to look at the toolkit and the recipe, this convenient distinction begins to break down in an odd way.

So let’s look at a fly leg or wing. I have it on the left and a limb bud here. And what’s interesting, if you can think about it, I’m just going to do an overview of it, the, the biological processes that determine the pattern of this, these appendages in three dimensions, that along this Z-axis, the Y-axis, and the X-axis here.

Let’s look at the tools that, that pattern that. Well, we already talked about some of these in the, in the limb, and I’m just showing a, a, a d- a drawing here which shows if you look at the X-axis, it’s really this ZPA with sonic hedgehog, and there’s another gene which I didn’t talk about, BMP. Um, if you look at a fly imaginal disc, which looks nothing like a limb bud at all, or the imaginal disc of a wing or a leg, um, they have a hedgehog gene that’s evolutionarily related to sonic hedgehog, and it is turned on in the entire sort of posterior, uh, p-

half of the, uh, of the, uh, of the, uh, of the developing fly imaginal disc. And there’s another gene, Dpp, which is ex- is turned on just along the margin here, and that, by the way, is s- the same gene as BMP if you could trace it in, in, in evolution, in, in, in evolutionary trees of genes.

What happens when you misexpress Sonic on the opposite side? You remember we showed that to you a million times. You get a, um, a duplicated fin or a duplicated limb.

What happens if you misexpress Hedgehog, its equivalent in the fly m- wing imaginal disc, on the opposite side, or even this Dpp? What do you find? You find a duplicated wing.

Okay, these are differently derived structures, but you find, uh, duplicate– same effect, same genes evolutionarily doing similar kinds of things, equivalent. And I could say the same thing for genes that are on the y-axis, which I’m not gonna get into. You have genes like wingless, which I didn’t draw, uh, apterus, and here you have genes that are wingless is here too, and LMX1.

And you also have in the z-axis, the axis which grows out, you have other genes which, uh, control the, the– which are, uh, within the AER, but actually are also controlling the, the outgrowth of the thing, uh, DLX here and Distal-less in the fly leg, but not in the wing. So really, if you look at it, and just the take-home messages is: here you have two organs which by all accounts are, are the dif- are different, okay, in an evolutionary sense. Yet the toolkit, the underlying toolkit that makes them, is actually looks to be very similar.

So similar in many ways that it may be the same in an evolutionary sense, that is continuous and doing something. This leads me to sort of the final sort of sequence of the talk, which is to really think about what this means with regard to the origin of organs. And there was an analogy, a flawed analogy, and but an analogy that was very powerful that was set up by François Jacob in 1977.

It’s the notion of, of tinkering. He took a very teleological view of evolution, so let’s just ignore that for a second. But he had a, um, he had a, an analogy that has, has some intuitive power.

And that is what he says, “Evolution, you know, doesn’t act as an engineer who can build structures from scratch.” In his mind, um, evolution acted as a tinkerer modifying existed o-odds and ends, Things that exist to make the new. Now, put in non-teleological terms, what it means is that the fuel, uh, for evolution, the variation that natural selection actually sort of acts on, is really the result of changes to the existing genetic structure in an organism, genetic and developmental structure in an organism.

It acts on what exists at every stage. And what exists in every stage are the genes and developmental processes, indeed much of the toolkit that’s making the organs of ancestral forms. So this leads me to sort of think about when I look at, uh, cladograms, um, you know, to think of something as, you know, how when we deploy this notion of, you know, the Hummer analogy, uh, we able, able to trace the structure of organs in one way, but also the toolkits that pattern them and aspects of those toolkits.

It makes one think of almost a biological cut and paste, and not as much as the Wall Drug jackalope or the Wisconsin Narrows bass cat. But, um, it leads to several different notions. The first is versions of the same toolkit pattern different organs.

Obviously, we’ve seen that with the fly wings and the limbs of vertebrates. We’ve seen that in fins and, uh, and gill arches. That ancient tools can be redeployed during the origin of new organs.

That may have been the case in the, in the origin of appendages themselves from the, from perhaps the gill arches of, of, uh, of, uh, of unfinned, uh, ancestors. And finally, and this is something that my, my introducer David Wake has talked about for a long time, that is having a common toolkit, having common processes that build bodies makes the independent evolution of similar structures more likely rather than less likely. When you– nobody’s really read Stephen Jay Gould’s, uh, final tome because it’s about seventeen hundred pages.

Uh, but I actually did. I was one of his, uh, one of the students who worked with him. He devoted two hundred pages, more than two hundred pages of his final book to looking at the consequences of conserved genes on parallel evolution.

And I really think he put his finger on the, uh, something that’s very important, that the independent evolution of similar structures is something that’s going to be made more common rather than less common by the unity of the toolkit that we see in diverse kinds of creatures. And this sort of allows us to return to our opening nose, and that basically answering the question that we can look at the nose, and we can say quite confidently looking at, um, looking at phylogeny, evolutionary history, we can say that the sort of the nasal organ of mammals is the same thing at the level of organs. Scientists are still undecided about this particular one.

Um, however, but yet it’s not the same thing as an organ in an evolutionary sense, It’s the beak of a, a bird and the proboscis of a paddlefish and the proboscis of a beetle. Yet despite that, as these things grow, as these things develop, they use the same general tools to, to form their, form their structures inside. So I want to close with the same series, the same sequence of things I talked about yesterday, and that is the power of thinking with trees.

We sh– You know, we tend– I tend even, when I’m presenting, to think about evolution and present evolution as a linear series of events, a gradual series that happens within one chain– one species with one set of organs changes into another species with another set of organs and so forth. But we really need to return to Darwin’s original vision, of which is actually original vision is right here, which is his notebook with w– his first tree, which says, “I think” here, um, to the notion of a tree Because the notion of a cut and paste becomes quite powerful because in the diversification of creatures and their evolutionary development of their evolutionary, uh, diversity from one another, from their common ancestors, as changes happen genetically within different populations, it will be more likely rather than less likely to see similar kinds of anatomical structures arise in different creatures. Oftentimes, what we’ll see is whole modules, whole, whole assemblages of the toolkit that makes bodies redeployed and turned on in new ways to make all kinds of new structures.

And I’d like to close just with a thought on integration and that in integrative biology. And I think in this context, we really have a, a a power to integrative biology. Because to understand the origin of new organs, we have new tools, and it’s really how we use those tools to ask our– answer our questions that’s so vitally important.

And we have fossils to tell us about the sequence of anatomical changes that exist in ancestral stra- states. We have embryology to tell us about how cells interact to build build, build organs. And now we have at our disposal understanding of genomes and genomics to understand the regulatory elements, the elements, the little pieces of DNA, and the pieces that bind to those pieces of DNA that, that actually control developmental events in different creatures.

Because it’s not trivial at all if we can link genomics, fossils, and embryos to understand how whole new toolkits can be redeployed to make whole new ways of, of, of, of, of living i-in an ecosystem. I’d like to thank and to close again by thanking my hosts, uh, here at Berkeley for a marvelous week, and I’d like to thank you for being such a great audience. Thank you very much.

(applause)

[00:51:54] PROFESSOR DAVID WAKE:
Thank you very much, Neil, for those, uh, excellent talks. Uh, if there are questions, I’m sure that, uh, Neil Shubin would be happy to respond.

[00:52:04] AUDIENCE MEMBER:
Can you comment a little bit on how far back in terms of, for example, going back into microbes, some of those developmental genes go?

[00:52:15] NEIL SHUBIN:
Oh, sure. I mean, you know, if you look at, um, If you look at the way, um, cells interact with their environment, uh, and the way that information from outside a cell is translated to inside a cell, which is such an important part of building bodies in terms of such an important part of interacting with the environment, virtually all that apparatus in some ways, way, shape, or form, can be originally traced to microbes. And I mean, that’s, you know…

So to really understand, uh, like Nicole King, who’s here at Berkeley, to understand the origin of bodies themselves, you really have to understand microbes ’cause that’s where many of these, these, these mechanisms first are, are, arise as microbes are doing their jobs being microbes, interacting with the world.

[00:52:58] AUDIENCE MEMBER:
So over the journey of your fossil discovery or finding, have you find any, um, vertebrate, vertebrate, uh, animals that have more than four sets of limbs, like six limbs, um?

[00:53:18] NEIL SHUBIN:
Um, no, I haven’t, but they exist. And so if you look at, um, it depends what you call a limb, but if you, um, uh, look at some sort of– there’s many kinds of these things called spiny sharks, what you’ll find is they can have multiple sets of paired appendages. Whether they’re the same thing as the true paired appendages that we have, I don’t know, but these are very sort of basal fish, and they have, uh, multiple sets, and they exist-

[00:53:38] AUDIENCE MEMBER:
Do you think if there is any explanation of why we don’t see any creature with more than four limbs in the wild?

[00:53:44] NEIL SHUBIN:
Well, you see it. Um, so, like, the whole… Remember multi-legged frogs? Remember the, um, where frogs would develop with, you know-

[00:53:51] AUDIENCE MEMBER:
Or something like dragons with wings.

[00:53:53] NEIL SHUBIN:
Yeah, right. So you actually see, uh, uh, mutations or you see perturbations in development that can produce a creature with lots of legs. The problem is they can’t get around, they can’t walk.

Those are not typically innervated, um, and they’re not coordinated within the central nervous system. So you can have a limb, but, you know, you may not have a limb that can be, uh, functional because it’s not part of the– wired into the central nervous system in any effective way. Um, and, uh, oftentimes they’re just dragging these things along, and it’s a liability.

Is the outcome of predation. Um, but that’s invertebrates. I don’t know what’s happening in invertebrates.

I just know the frog world. Yeah.

[00:54:25] AUDIENCE MEMBER:
Um, you, you showed a, um, slide of the fellow who said, uh, gill arches explained also the jaw and other parts, and that seemed very similar to what, um, say fifty years earlier than that, Goethe had said, about, um, what about, um, plants, plants where everything was basically a whorl of leaves, and they just developed into petals or stamens or, or, um, the, um, ovaries. Um, so I’m curious, why did– um, given that, that idea seemed to be somewhat accepted, why did they, um, uh, feel that the Gill Arch fellow was ignored?

[00:55:08] NEIL SHUBIN:
Yeah, the, the answer is three words: Francis Mayn- Maitland Balfour, who, uh, was one of the greatest embryologists of all time, uh, worked on shark embryos. He was a, um, a professor of embryology at Oxford University and had an alternate theory, which is called the fin fold theory, that these fin– that the paired appendages arose initially as a fold across the body. And he marshaled a whole lot of, um, circumstantial evidence for it, but no direct.

He had no embryo with a true fin fold. But he was very, very, very persuasive because he was so right on so many things throughout his career. Um, so much can be traced to Balfour that to some extent that, uh, that, uh, um, led to the demise of the gill-arch theory.

But also you’ll see, um, uh, uh, a fin fold that, that Balfour, uh, uh, proposed in some creatures, but not the creatures at this particular level of the phylogeny. But Goethe was, you know, this was a, this was a cottage industry, and a very powerful cottage industry. I sh- I don’t wanna use that word.

That’s actually a bad pejorative. But it’s actually was a very powerful way of looking at biology to reduce complex structures to their sort of essences. And that’s what people like Goethe were doing, uh, with heads being, you know, sort of re-redesigned vertebrae, uh, and the, the notion of flowers and so forth.

And all of, uh, Saint-Hilaire’s, uh, uh, laws of form we’re really trying to distill unbelievable diversity to very simple essences. And it really wasn’t until Darwin came along that we, you know, we, we don’t need these philosophical es-essences. We can actually find the ancestors or infer them from the findings we make.

[00:56:36] AUDIENCE MEMBER:
Uh, you talked about, uh, with appendages, there’s been a pattern of the one bone and two bones. Uh, why was that pattern so pervasive? And with the toolkit being independent, uh, and with parallel evolution, has there been any derivations from that?

[00:56:52] NEIL SHUBIN:
Yeah. The, the, the one bone, two bone things, you know, why– what, what advantage it offered, I don’t know. Um, if you look at the creatures that have it in the fossil record, it’s a marvelously mobile fin.

I mean, when you– th-you’re comparing it to something that has lots of, uh, bones at the base, which serves as really sort of con– a hydrofoil or a planar form, very well, having multiple bones at the base. Having one bone at the base actually gives you the chance to do an extensive series of, you know, uh, protraction, retraction, rotation. You know, if you had multiple bones at the base, throwing a baseball would be a whole lot harder.

So it seems to be it’s related with, initially at least, to the mobility, I’m just speculating, of the, of the, um, proximal area.

[00:57:31] AUDIENCE MEMBER:
Hey, um, hi, Professor. Um, so, uh, you showed the pictures of like the, uh, the the gill structures and the, um, and the like the jawbone and the ear bone in humans. So with what degree of certainty can you make these sort of connections, um, when you do this kind of study?

[00:57:46] NEIL SHUBIN:
Yeah, I mean, one of the things I’ve gotta tell you when– that absolutely blew me away when I was a student was seeing the transformation of jawbones to ear bones in the fossil record, uh, in the mammal-like reptiles. And that’s actually what initially almost attracted me to work on Triassic age rocks, which is at the origin of mammals where much of that transition happened. It really can be traced very powerfully, and there’s several lines of evidence that do it.

Number one is the embryology. Number two is the genetics. That is, there’s a genetic signature to each of these arches that’s present in the arches of fish, but also in the ear bones of, of mammals.

It’s also in the innervation of these things. The first arch structure in both cases, which is mandibular, has a certain type of innervation that’s different from the second arch structure, which is the facial nerve and so forth. So it’s written deeply in the comparative anatomy, in the muscles, the nerves, the arteries, the bones, in the developmental processes that produce them, in the, in the genes that specify that developmental process.

I mean, it’s really kind of be– I’m frothing at the mouth, it’s so beautiful.

(laughter)

[00:58:46] AUDIENCE MEMBER:
Yeah, uh, two, two quick questions here. First, if at least the cartilaginous components in the shoulder are possible gill arch derivatives, um, any thoughts on where the cartilaginous components in the hip may evolve from?

[00:59:03] NEIL SHUBIN:
Yeah, good question. I don’t know. I mean, it’s, um, uh, don’t know about the hip, And in fact, that touches on don’t know about how the rear appendage would form.

You know, uh, if you look at the fossil record, it’s p– The, the first paired appendages to appear in the fossil record are the front ones, and the pelvics appear later. That’s what you see in the fossil record when you look at jawless fish.

It may very well be once this sort of subroutine, genetic subroutine toolkit, whatever you wanna call it, that patterns the, uh, appendages arose in the pectoral fins, it was by some regulatory interaction, tissue specific and so forth, um, turned on in the hind limb to make a, you know, a hind fin. And so, um, I don’t know. The, the, the short answer is I don’t know the answer to that, but it may very well be a cooption of an existing genetic toolkit which was derived from the front fin.

[00:59:49] AUDIENCE MEMBER:
And then, uh, secondly, drawing upon this point of parallel evolution where developmental constraint, uh, or so-called channeling may, may predispose or bias the production of certain organs. Where in constructing evolutionary relationships, understand– understandably, it’s important to use independent characters. But if in development at many different hierarchical levels, structures could be linked.

Um, how do you think– what do you, uh, consider to be the implications of that–

[01:00:20] NEIL SHUBIN:
Do molecular phylogenies? You use, uh, you know, do your trees with molecular data. I mean, morphological data’s gonna be, in some cases, not all, I mean, it’s,

it’s wonderful in a lot of cases, I use it all the time, um, is going to be very powerful. But there are cases when you’re gonna have extensive homoplasy, and I’ve, I witness it frequently when we work on salamanders. Uh, you know, there’s a–

I didn’t read the paper, but there’s a paper that came out in Nature yesterday on showing that, you know, uh, feathered dinosaurs are not only in the theropod lineages, but ornithischian lineages. Finger-like structures appear not only in, uh, in creatures like Acanthostega and in a proto-form in Tiktaalik, but also in cr- creatures further down the tree in Ceratopteris. So you see parallel evolution quite a bit.

You know, it’s just we sort of sometimes are not as tuned to it because we have an agenda of making a tree. Uh, and it really, it is only in the way for us, but in reality, there may be a very strong biological signal there that tells us it’s quite a bit.

[01:01:13] AUDIENCE MEMBER:
I was wondering why soaring birds such as gulls and albatross have pointy wings and soaring birds such as buzzards have more or less rectangular wings.

[01:01:22] NEIL SHUBIN:
I’m sure there’s an answer to it of somebody who works on bird flight, but I’m not. You know, I’m, I’m, I’m a fish guy, sorry.

(laughter)

I can make up a story, but I will not do it with colleagues in there who will absolutely correct me immediately.

(laughter)

If they weren’t here, I’d give you a good story, I promise you.

(laughter)

[01:01:38] AUDIENCE MEMBER:
Uh, in your first lecture, you mentioned then the transition from, uh, water to land happened at only once. What are the evidences that it did really happen at only once?

[01:01:48] NEIL SHUBIN:
Yeah, that’s an awesome question because, you know, if parallel evolution’s the rule, maybe it happened multiple times. Um, the thing about it is the, the reason why we th- think it only happens once is ’cause the number of characters, characteristics we can use on the evolutionary tree as evidence to support that view, that evolve across the body. So if there was parallel evolution in the way, it would have to be body-wide and multiple systems, uh, from the vertebrae to the head to the limbs, the shoulder, and so forth.

So at– our evidence for that is the, the characteristics, the multiple, large number of them that support the evolutionary tree, um, that suggests only once. Um, I should say that embryologists, uh, in, uh, the ’30s thought it happened at least twice, once in salamanders and once in the lineage that led to, uh, frogs and amniotes, creatures that, you know, that develop in eggs. So, um, but no, the evidence is the characteristics that we use to make trees, and there’s a lot of them in that case.

They’re pretty…

[01:02:47] PROFESSOR DAVID WAKE:
Please join me in thanking Professor Shubin for these two outstanding lectures.

[01:02:52] NEIL SHUBIN:
Thank you.

(applause)