Reviewing From Extraterrestrials to Animal Minds by Simon Conway Morris: Full series

Full series on From Extraterrestrials to Animal Minds: Six Myths of Evolution by Simon Conway Morris.

Introduction and overview

Chapter 1: The Myth of No Limits — Part 1 — Part 2

Chapter 2: The Myth of Randomness

Chapter 3: The Myth of Mass Extinctions

Chapter 4: The Myth of Missing Links

Chapter 5: The Myth of Animal Minds — Part 1 — Part 2

Chapter 6: The Myth of Extraterrestrials

Final comments and reflections

Missing links are a myth, but whose? Chapter 4 of From Extraterrestrials to Animal Minds

There are some truly vexing and annoying myths of evolution. They are almost exclusively recited and embellished by religious propagandists, some of whom actually know what they're doing. Rarely but notably, there are myths that are gleefully repeated by creationists while being amplified by scientists who should know better. The clearest example of this is the mythology and nonsense surrounding "junk DNA."

Missing links are not an example of this.

The phrase "missing link" is so dated and so scientifically laughable that it could only be seriously discussed in a book about myths that circulate among laypeople who watch YouTube videos about Sasquatch, refuse vaccines to own the libs, and go to church. What is it doing in a book by Simon Conway Morris, a book that claims to address "areas of received wisdom that are long overdue for careful reexamination"? It's the subject of the fourth chapter of From Extraterrestrials to Animal Minds: Six Myths of Evolution, "The Myth of Missing Links."

The Mórrígan. A myth.

This question summarizes one source of my deep disappointment in this book, a work that has lowered my opinion of its author. I have no right to blame my disappointment on the author, and I know that my feelings betray an expectation on my part that the professor has no obligation to even consider. That expectation: that Christian scientists acknowledge and consider resisting the mountains of lies that their fellow believers dump into the world.

Common ancestry, bottlenecks, and human evolution

Human evolution has been in the news quite a lot recently.

• New genetic data suggest that ancient humans included both Neanderthals and Denisovans, which colonized different parts of the world but subsequently interbred with so-called modern humans and left telltale traces of this history in the genomes of living humans.
• New analysis of current genetic diversity suggests that human population size underwent interesting fluctuations throughout the history of our species, but concludes that the population never dipped below a few thousand reproducing individuals.

Unsurprisingly, these findings have been discussed in the context of Christian views of human origins. In the context of some of these discussions (among Catholics, for example), I have noticed some confusion regarding the implications of common ancestry. I will illustrate the error with a stylized example, then explain why it is an error.

New limbs from old fins, part 2

Titktaalik roseae.
Image from
https://tiktaalik.uchicago.edu/index.html

The second post in my series on limb evolution is now up at the BioLogos site. This installment reviews the fossil evidence on fin-to-limb evolution, introducing the famous Tiktaalik. Next up: evidence from developmental biology.
The first post at BioLogos outlined limb structure and some historical background. The series at BioLogos was spawned by an idea here at QoD, which aimed to discuss some new findings in the fins-to-limbs story. Those new findings will be discussed in the final installment of the series at BioLogos.

*Edit July 2020: The series was consolidated into a single article on the BioLogos site. The link now goes to that single article.

New limbs from old fins, part 1

Last month, I started a series on the topic of limb evolution, here at Quintessence of Dust. That series has been transformed (through a series of intermediates) into a series of posts* at the BioLogos site. The first installment is now up, and it provides an expanded introduction to the topic and a little historical context. Subsequent posts will tackle fossils, developmental biology, genetics, the explanatory role of design, and related themes.

So go check out the introduction, and feel free to contribute comments, questions and suggestions here. And enjoy the image below, from Wellcome Images, which is featured in the post at BioLogos. Cool, huh?

*Edit July 2020: The series was consolidated into a single article on the BioLogos site. The link now goes to that single article. 

Molecular evolution: improve a protein by weakening it

In the cartoon version of evolution that is often employed by critics of the theory, a new protein (B) can arise from an ancestral version (A) by stepwise evolution only if each of the intermediates between A and B are functional in some way (or at least not harmful). This sounds reasonable enough, and it's a good starting point for basic evolutionary reasoning.

But that simple version can lead one to believe that only those mutations that help a protein, or leave it mostly the same, can be proposed as intermediates in some postulated evolutionary trajectory. There are several reasons why that is a misleading simplification – there are in fact many ways in which a mutant gene or protein that seems to be partially disabled might nevertheless persist in a population or lineage. Here are two possibilities:

1. The partially disabled protein might be beneficial precisely because it's partially disabled. In other words, sometimes it can be valuable to turn down a protein's function.

2. The effects of the disabling mutations might be masked, partially or completely, by other mutations in the protein or its functional partners. In other words, some mutations can be crippling in one setting but not in another.

In work just published by Joe Thornton's lab at the University of Oregon*, reconstruction of the likely evolutionary trajectory of a protein family (i.e., the steps that were probably followed during an evolutionary change) points to both of those explanations, and illustrates the increasing power of experimental analyses in molecular evolution.

Design and falsifiability

Last month I had an interesting conversation with Casey Luskin of the Discovery Institute (DI), at Evolution News and Views (ENV), a DI blog/site that recently opened some articles to comments. The topic of the original post was common ancestry in humans and other primates, but Casey and I discussed various aspects of design thought.

One subject that came up was the falsifiability of design. I maintain that design arguments, whenever they also postulate the existence of an omnipotent deity (or any super-powerful being, for that matter), are inherently unfalsifiable. And I want some feedback on my argument.

Exploring the protein universe: a response to Doug Axe

One of the goals of the intelligent design (ID) movement is to show that evolution cannot be random and/or unguided, and one way to demonstrate this is to show that an evolutionary transition is impossibly unlikely without guidance or intervention. Michael Behe has attempted to do this, without success. And Doug Axe, the director of Biologic Institute, is working on a similar problem. Axe's work (most recently with a colleague, Ann Gauger) aims (in part, at least) to show that evolutionary transitions at the level of protein structure and function are so fantastically improbable that they could not have occurred "randomly."

Recently, Axe has been writing on this issue. First, he and Gauger just published some experimental results in the ID journal BIO-Complexity. Second, Axe wrote a blog post at the Biologic site in which he defends his approach against critics like Art Hunt and me. Here are some comments on both.

It's just a stage. A phylotypic stage. Part III: Fish and more

Given that disputes over the existence and meaning of the phylotypic stage and the hourglass model have simmered in various forms for a century and a half, the remarkable correspondence between the hourglass model and gene expression divergence discovered by Kalinka and Varga and colleagues would be big news all by itself. But amazingly, that issue of Nature included two distinct reports on the underpinnings of the phylotypic stage. The other article involved work in another venerable model system in genetics, the zebrafish.

The report is titled "A phylogenetically based transcriptome age index mirrors ontogenetic divergence patterns" and is co-authored by Tomislav Domazet-Loso and Diethard Tautz. To understand how their work has shed light on the phylotypic stage and the evolution of development, we'll need to look first at an approach to the analysis of evolutionary genetics that these two scientists pioneered: phylostratigraphy.

It's just a stage. A phylotypic stage. Part II: The flies

The controversy about the existence of the phylotypic stage is more than some bickering about whether one blobby, slimy fish-thing looks more like a Roswell alien than another one does. It's about whether the phylotypic stage means something, whether it tells us something important about development and how developmental changes contribute to evolution. To answer such a question, we need more than another set of comparisons of the shape and movements of embryos and their parts. We need a completely different way of looking at the phylotypic stage, to see if something notable is going on under the hood. So vertebrates all look the same at the tailbud stage. What does that mean?

Embryos look the way they do because of the positions and behaviors of the cells that make them up. The cells in an embryo all have the same DNA, and the link between that DNA and those specific cell behaviors is the basic process of gene expression. (This is a fundamental principle of developmental biology.) And by gene expression, we usually mean the synthesis of messenger RNA under the direction of genes in the DNA. Different cell types express different sets of genes, and the orchestration of the expression of particular genes at particular times is a big part of what makes development happen. When considering the phylotypic stage, then, developmental biologists wondered: is the apparent similarity of embryos at that stage reflected by similarities in gene expression. Or, more specifically, does the hourglass model hold up when we look at gene expression? This was the focus of the two articles in last Friday's Nature that inspired the cool cover.

It's just a stage. A phylotypic stage. Part I.

Disputes and controversies in science are always a good thing. They're fun to read about (and to write about), and they're bellwethers of the health of the enterprise. Moreover, they tend to stimulate thought and experimentation. Whether scientists are bickering about evo-devo, or about stem cells in cancer, or about prebiotic chemistry, and whether or not the climate is genial or hostile, the result is valuable.

Now of course, some controversies are invented by demagogues for political purposes. The dispute in such cases is far less interesting and clearly less profitable, even if participation by scientists is necessary.

This week, two papers in Nature weighed in on a major scientific controversy that has its roots in pre-Darwin embryology, fueled by some gigantic scientific personalities and even tinged with what some would call fraud. This intense scientific dispute spawned a sort of doppelganger, a manufactured controversy that is just one more invention of anti-evolution propagandists. The Nature cover story gives us a great opportunity to look into the controversies, real and imagined, and to learn a lot about evolution and development and the things we're still trying to understand about both.

Signature in the Cell: Chapters 9 and 10

"He..strikes at randome at a man of straw."
– Richard Saunders, A Balm to heal Religious Wounds, 1652. Quoted in the Oxford English Dictionary, 2nd Edition

"An imaginary adversary, or an invented adverse argument, adduced in order to be triumphantly confuted."
– Second definition entered for "man of straw" in the Oxford English Dictionary, 2nd Edition

Chapter 9 is called "Ends and Odds." Chapter 10 is "Beyond the Reach of Chance." Between them, they advance a straw man so idiotic that I wonder whether Meyer will be able to reclaim any significant intellectual integrity in the chapters that follow. I've already noted that this is not a book of science or of serious scholarship. Now it seems that it doesn't even merit the distinction of popular science or pop philosophy. These two chapters have purely propagandistic aims, and they do serious damage to the book's credibility and to the author's reputation. Meyer has shown his cards.

Carnival of Evolution 14

Welcome to Quintessence of Dust and to the 14th Edition of the monthly Carnival of Evolution. Thanks for stopping by, and for supporting scientific carnivalia, members of a taxon that seems to be flirting with extinction.

One good reason to visit a carnival: brain stimulation. Brain Stimulant offers some thoughts and speculations on Free Will and the Brain, touching briefly on themes of selection and adaptation, and he doesn't charge as much as the clinic would.

Another good reason: you can bump into real scientists, the kind who actually work on evolution. Ryan Gregory has a day job as an expert on genome evolution, but somehow finds the time to blog at Genomicron. Recent entries there include fascinating pictures of ongoing field work. For this month's carnival, be sure to read two reviews of the ideas of Stephen Jay Gould, focusing on controversial papers by Gould published in 1980 and 1982. You may find that you have been misinformed about Gould's positions, and you'll surely learn more about evolution.

Michael White at Adaptive Complexity is another blogging scientist, and he writes very clearly about parasitic DNA in Selfish Gene Confusion.

David Basanta is a biologist who runs a cool blog called Cancerevo: Evolution and cancer, which is subtitled "Studying cancer as an evolutionary disease." Check it out, and don't miss his recent piece on Stem cells and ecosystems.

Zen Faulkes is a biologist who blogs at Neurodojo. That's cool enough, but the subtitle of that blog is "Train your brain." Hey, this could be a theme for the whole carnival! He recently wrote about a walking bat in New Zealand. Bat evolution...we can't get enough of that. I've written about it myself.

Brains and their origins come up in an extensive discussion of early animal evolution at AK's Rambling Thoughts. The post is The Earliest Eumetazoan Progression.

At The Loom, the peerless Carl Zimmer discusses AIDS in chimps and the relevance of the story to conceptions of scientific progress. AIDS and The Virtues of Slow-Cooked Science is engrossing and important. And John Wilkins discusses some new fossil apes in an excellent recent post at Evolving Thoughts.

John Lynch reviews a new book on Alfred Russell Wallace. Caveat lector. Brian at Laelaps takes us on a historical tour of the work of Florentino Ameghino. Are those elephants or not? Brian's discussion is typically excellent.

At The Spittoon, AnneH discusses new findings concerning both the past and the future of the mammalian Y chromosome.

Hoxful Monsters is a future host of this carnival; Nagraj recently reviewed some recent work on pattern formation in the development of spiders. Wonderful evo-devo stuff.

Someone at Wired wrote some swill about the "10 Worst Evolutionary Designs" which annoyed a few smart bloggers. At Deep-Sea News, Dr. M sets the record straight. The title is self-explanatory: Worst Evolutionary Designs? No! Brilliant Solutions to the Complexity of Nature and Constraints.

Larry Moran at Sandwalk is attending a conference entitled Perspectives on the Tree of Life. He's posted reviews of days one and two so far.

And that's our carnival. Thanks for reading, and on the way out I hope you'll look at my nearly-complete series on Notch and deep homology.

Next month's edition will appear at Southern Fried Science. To submit posts, use the submission form found at the Carnival of Evolution site. And if you like the carnival, help us promote it with a link, and/or consider hosting. More info at the carnival site.

Deep homology and design: why Notch?

The Notch signaling pathway is a golden oldie of genetics in two ways. First, it's a system that was first described at the dawn of modern genetics – named by its founder, Thomas Hunt Morgan – and used to establish some of the most basic principles of "the physical basis of heredity," as Morgan put it. (His book by that title is a founding document of modern genetics, describing in 1919 what we now call chromosomes without any knowledge of their chemical makeup.) Second, it's a system now known to be as ancient as animals themselves.

Why Notch? The name refers to the appearance of some of the first mutant fruit flies described by Morgan and his colleagues in their famous work in the early 20th century. They found flies with notched wings, and found that the trait was dominant.

Figure 1 from T.H. Morgan, "The Theory of the Gene." American Naturalist 51:513-544, 1917.

So aside from its importance in evolution and development, Notch is of historical interest to genetics. Now, Morgan was interested in Notch (the gene name is capitalized because the original trait is dominant, in case you're wondering) because of its mode of inheritance, not specifically because of its biological effects. (I mean, who cares about flies with notched wings?)

But twenty years later, things got more interesting when a different mutation in Notch was found to cause a weird (and lethal) overgrowth of the nervous system. Interesting... then, as geneticists began to probe the genetics of animal development 50 years after Morgan's initial discoveries, using the fruit fly as a model, Notch started turning up again and again. Problems in Notch signaling led to developmental problems all over the place: brain, eyes, gut, wings, bristles.

By the beginning of the 1990's, geneticists had figured out why its activity is so central to proper development: Notch controls a crucial type of cell-to-cell interaction that leads to a change in cell fate. And they had found Notch signaling in animals of every kind, including in humans, mediating the same kinds of inductive developmental interactions. It's not as complicated as it might sound – in such an interaction, two cells interact physically (they have to touch) and after the interaction one or both of the cells changes its developmental fate, choosing to become, say, a nerve cell or a skin cell. That weird brain overgrowth in the flies with no Notch activity results from a failure of cells to communicate in this way, such that all the cells on the outside of the fly's head become brain cells. (Flies, like most animals, prefer to have some skin over their brains, but in these mutants there's very little skin and lots of extra brain. Ick. See Figure 1 of this recent paper in BMC Biology for pictures; the green stain indicates nerve cells and the second animal down has the nasty trait.)

The point is that Notch signaling involves direct cell contact, and typically leads to cells making decisions about what to do when they grow up. So how does it work? Well, we know an awful lot about this particular system, and there are myriad details of mechanism and control that I'm going to skip. The very basic outline is as follows. Some cells make the Notch protein, which is a receptor. Other cells make the Delta protein, which is the signal that activates the receptor. (One useful analogy is that of locks and keys: Notch is the lock, Delta is the key.) Both proteins are displayed on the cell surface. When the two cells come into contact, the Delta protein on one cell activates the Notch protein on the other. When Notch becomes activated, it gets chopped into at least two pieces. One piece leaves the surface of the cell and travels inward to the nucleus of the cell. There, in collaboration with other proteins, it causes changes in gene expression, meaning that some genes are turned on or up and others are turned off or down.

This mode of signaling is unique and extraordinary. What we have is a signaling system that takes cell-to-cell contact and converts it directly into changes in gene expression.

Now, let's think carefully about this. We have a system of receptors and activators, in the form of Notch proteins (there are at least four in humans) and Delta proteins (there are several in humans, in a few different protein families), which serve a critical and unique purpose in cell-to-cell signaling. The function is conserved in all known animals, and that's not surprising – having cells send messages to their immediate neighbors, directing them to adopt particular fates, is key to constructing tissues and organs. I hope you'll agree that we should expect to see these inductive mechanisms in the development of complex organisms. More to the point, one should expect this regardless of one's stance on questions of "intelligent design."

Here's what is surprising. The same Notch proteins are used for this purpose in every known animal. And here's why that's surprising: as far as we know, there's no reason to insist on those particular proteins playing those particular roles. It's easy to envision – and then design and create – a set of locks and keys that bear no resemblance to Notch or Delta but that can accomplish these somewhat basic purposes just as well. There's no need for such a specific solution to a basic challenge. Why does every animal use Notch? Recall the previous post in this series and how we approached this question of common design. Here, again, are our options.

1. These inductive signaling events could only be accomplished by Notch. There is a design constraint, currently unknown, which forces that choice. It may seem that the system could have been effectively constructed using a different lock-and-key combination, but in fact it could not function (or function well) any other way.
2. These inductive signaling events could be mediated in various ways, but the choice of Notch has been forced by common ancestry. The earliest animals settled on this choice, and their descendants have used it ever since.
3. These inductive signaling events could be mediated in various ways, but an intelligent designer has repeatedly chosen Notch for reasons known only to her/him/it.

Option #1 is, in my view, unreasonable. The system is not complicated in its basic design. There are no clear constraints on the choice of lock and key. A designer who is crafting an organism from the ground up need not select that particular lock/key combination, and someone who intends to argue otherwise needs to demonstrate how that particular combination is superior.

Option #3 is, I think, perfectly reasonable. The only problem is that one must know quite a lot about the designer to begin to surmise her/his/its goals and proclivities. Without that knowledge, it is no more reasonable to assume a preference than it is to assume a constraint.

The point is not that we can ever rule out preferences or other characteristics of a creator or designer. The point is that we can rarely make explanatory use of them. Consider that while we may assert that the Creator/Intelligent Designer prefers that pine trees have needles, we would not advance that as a useful explanation for why pine trees have needles. Specifically, we would never advance that as an alternative explanation in place of one that notes that today's pine trees have the same needles that last century's pine trees had, by virtue of biological ancestry.

Notch signaling represents one of the classic examples of deep homology. It seems to me that design theorists need to deal with deep homology before they can ever be taken seriously as scientific thinkers. Deep homology is crying out for explanation, and those who believe that the biosphere cries "design" are remiss in not offering a serious design-based explanation for the fact that every animal on the planet uses the same lock-and-key mechanism to achieve basic cell-to-cell inductive communication.

Next, we'll look at a recent and very interesting example of new findings that illustrate the striking conservation of Notch-mediated developmental events – an example of deep homology that could arise from the very root of animal ancestry.

Deep homology and design: common design and its implications

Consider these not-so-random samples from the animal world: a cockroach, a zebrafish, a mouse. What do these creatures have in common?

Left to right: American cockroach (Periplaneta americana), zebrafish (Danio rerio), house mouse (Mus musculus). Cockroach image from Wikimedia Commons, zebrafish and mouse from Wellcome Images.

Well, they're all animals and that means they're all eukaryotes, for example. They all have DNA-based genomes. They all like water to some extent. They all have muscles that cause them to move. And so on.

But let's think of them in a different way. Let's think of them as things that exhibit design. (Not Design. Just design.) We see similarities like the ones we just listed, and we see some dramatic differences. Insect, exoskeleton, open circulatory system. Fish, gills, egg-laying. Mammal, milk, hair, live birth, temperature control. We can see elements of common design (limbs and joints, eyes, nerves) and elements of specialized design (lungs, fins, antennae).

Now let's forget everything we know about common descent and adopt an Intelligent Design perspective. This isn't hard to do: just think of each animal as a machine that was designed to be the way it is. The machines have some common design elements and some specialized design elements. Now this is important: let's assume that each machine was designed separately, such that design decisions were made on a case-by-case basis (for each type of machine, not for each individual machine). In other words, let's think of the cockroach as designed from the ground up to be a cockroach, and the fish and the mouse likewise. Simple, right? I think so.

Now, let's look under the hood of each machine and ask detailed questions about how it's built, again with the assumption that it was designed. Not just its overall structure, but also the procedures used for its assembly. Let's look, in other words, at its molecular machinery – machinery for signaling between cells and tissues, machinery for signaling within individual cells, machinery for directing gene function during development and normal function. And let's focus specifically on the signaling systems in these creatures and in their developmental stages. What would we expect to see? Well, let's consider some basic scenarios.

1. Maybe the signaling systems will be roughly the same – or even largely the same – in all three animals. This would imply that such systems are hard to assemble and perhaps even harder to tune and maintain, and therefore we would conclude that there are very few ways to make a working system. The only other explanation would refer to preferences on the part of the designer, who was unconstrained by design limitations but nevertheless insisted on doing things a certain way.

2. Maybe the signaling systems will differ between the three animals, to such an extent that it is clear that the choice of a system is somewhat arbitrary, arbitrary in the sense that the choice of a particular system is largely independent of the context or the function that is specified. The implication is that there are plenty of ways in which cells and molecules can communicate, and no strong constraints on the designer's choices.

Now of course we may find examples of both scenarios in our analysis. Perhaps some signaling systems will appear to be highly constrained while others will be largely different among the three species. The point, though, is this: when examining machines that were separately designed, common design implies either design constraint or designer preference. Divergent design implies a lack of design constraint. There are no further options: either the designer was constrained, or she wasn't; if unconstrained, she could nevertheless choose a favorite scheme and leave the impression that she was somehow constrained.

Designer constraint could arise in various ways. It could be that a particular signaling system is uniquely suited to a particular purpose. It could be that a particular signaling system is highly robust to damage or other challenges. It could be that there are only a handful of different possibilities due to limitations in the raw materials. One variation of that last possibility would look a lot like how evolution is known to work: the designer tweaks the system a little at a time, working with the materials supplied by each generation and therefore constrained by common descent.

Design proponents can be stunningly cavalier about all this. "Common elements in animal biology? Well of course! Common design!" But wait: common design implies either design constraint (that was the best way to do it – or the only way to do it) or designer preference (she just happens to like it that way), and those are dramatically different from an explanatory standpoint.

It turns out that signaling systems in animal development are so universally conserved that they require an extraordinary explanation. The commonality of the elements is so striking that it took most biologists by surprise when it first became evident, and remains one of the most remarkable facts of developmental biology today. We'll look at some recent advances in this area of evo-devo in posts to come.

But one last thing: I'd like to try a thought experiment to illustrate how we might approach questions of signaling in animal cells and embryos. Consider a group of 50 people who have agreed to help with your experiment. You divide them into pairs and tell each pair to send one person out of the room. Then you tell the remaining people to greet their partners upon their return, using a single word of their choosing that is certain to convey the greeting. You observe that all of the people employ either "hello" or "hi" for this purpose.

Question: would you conclude that "hello" and "hi" are uniquely suited for the task, and that no other word could possibly have worked? I hope you would seek another explanation and perhaps consider trying the experiment in, say, Shanghai or Guadalajara. You would conclude, I wager, that the word itself is of little explanatory value. In other words, the choice of a word was constrained, but not by anything specific to the word itself. In Shanghai, it's "ni hao." Maybe somewhere it's "duuuuuuude." And in a matter of minutes, you could change it to "ahoy" or "blorp" or anything you want.

And if you really wanted to probe the notion of constraint in human conversation, you would ask your 25 pairs of subjects to come up with an identifying word or phrase that they could call out to find each other in the dark. You would find, of course, that the choice of that word or phrase would be almost completely unconstrained.

What does all this have to do with signaling systems and design? That's for next time. Till then, blorp.

Deep homology and design: a new series

Recently I was reading a superb review article [doi] on the subject of a famous and important cellular signaling pathway called the Notch pathway. The author, Mark Fortini of Thomas Jefferson University, quoted James Puckle (an 18th-century English inventor and writer) on the "wonderful frame of the human body" in which "so many strings and springs" which all must "be in their right frame and order" for life and concluding that "it is next to a miracle we survived the day we were born." (If you must know, it's maxim #914 in The Club, in a section called "Death.")

This reminded me of some personal tragedy in our own family, after which Puckle's conclusion was repeated almost verbatim. It also reminded me of my need to write about the amazing homology of developmental signaling mechanisms in animals. For many months, I've listed an article on "deep homology" as the subject of my next Journal Club. But this topic won't fit into one article review, so I've decided to turn it into a little series.

Here's what Fortini writes in his introduction, after quoting Mr. Puckle:

Surprisingly, research over the past few decades has revealed that the orderly differentiation and arrangement of these many physiological ‘‘strings and springs’’ are controlled by a relatively small number of developmental signaling pathways. These pathways, including the Notch, Ras/MAPK, Hedgehog, Wnt, TGFβ, and JAK/STAT pathways, among others, are widely conserved throughout the animal kingdom and they cooperate throughout development to pattern a diverse array of tissues in different animal species.

The lingo might seem strange, but I hope the point is clear. The vast diversity of animal life, with "endless forms most beautiful," is assembled through the action of a small set of signaling systems. And, remarkably, the systems are used in the same ways in animals that couldn't be more different in behavior or structure.

This fact raises interesting questions about design and evolution. Why so few systems? Why are they used again and again, for the very same purpose? Are these choices forced by design constraints of some kind, or is there another explanation? Could it have been otherwise? Can it be otherwise? I'll tackle those questions while discussing some recent experiments in evolutionary developmental biology, or evo-devo.

And what of this phrase "deep homology"? It was coined by some of the founding minds of evo-devo – Neil Shubin, Cliff Tabin and Sean Carroll – as they considered the fact that animal limbs of every kind are "organized by a similar genetic regulatory system that may have been established in a common ancestor." And we mean limbs of every kind: whale flippers, fish fins, bat wings, human arms, and, amazingly, insect limbs. Such disparate structures may not be evolutionarily homologous (meaning that they were modified from a common ancestor) but the signaling systems that create them are homologous.

This, then, is deep homology: the sharing of signaling mechanisms that are used to create diverse (though often functionally similar) animal structures. So please join me, and maybe we'll lure interesting commenters into the discussion.

Why I'm not a Behe fan: conclusion and a challenge

About 2 months ago, I finished a series on Michael Behe's latest book, The Edge of Evolution. I concluded that it was a terrible book, displaying significant errors of both fact and judgment. The book's main argument is a population genetics argument, and Behe seems to have little knowledge or understanding of that difficult subject. The book is a joke, and I believe it will someday be seen as one of the more disastrous mistakes made by the ID movement. But I think it's important to distinguish between Behe's errors (which reflect on his scientific credibility and on his decision-making habits) and his thesis. His book is full of mistakes, but that doesn't mean that his proposal is known to be false. So I'd like to make it clear what my verdict on his book actually is, then present an outline of one way to actually test Behe's hypothesis.

1. In The Edge of Evolution, Behe correctly identified a biological process – the generation of genetic variants that lead to evolutionary change – as a likely focus of deliberate design. Having concluded that common descent is true, he reasoned that the trajectory of change through the tree of life might be expected to show evidence of non-random direction. Design, as he and others in the ID movement conceive it, might be manifested in the pattern by which the tree of life came to be. (Some might go as far as to say that it must be manifested in such a way, but I don't think Behe suggests this.) My point is that there is nothing stupid, irrational, or unscientific about Behe's reasoning. So, Behe conceived a hypothesis, which I will restate as follows:

• Based on the consideration of life's complexity, specifically on the consideration of the integrated complexity that characterizes the molecular machinery of the cell, it is proposed that random mutation and subsequent selection cannot fully account for the evolutionary development of biological systems.
• Consequently, it is proposed that the process of mutation is non-random.

Again, I find nothing outrageous or stupid about the hypothesis, or even its rationale. Molecular machines are astoundingly complex and integrated, and I do think it's reasonable to wonder how such things can come about without the aid of a superintelligence. In other words, Behe's proposal is not inherently incoherent or otherwise easily dismissed. Might the machinery of life have emerged through non-random processes? Sure. EoE is a joke, but not because the proposal is a joke.

EoE is a joke because Behe seems not to have even attempted to establish the strength of the hypothesis. Very little of the book is devoted to this central concern, and those sections that take up the task are so laughably wrong that they have led me to question Behe's scientific integrity. (Sorry, no apologies: the errors are too basic, and the proposal too world-altering, to give someone who is vying for scientific immortality a pass on standards of scientific conduct.)

But this is important: Behe's failure to even attempt an honest defense of his proposal does not imply that the proposal has been falsified. It hasn't. It remains possible that the development of biological machines – especially in the early days of the tree of life – was characterized by a non-random, directed trajectory. (I happen to doubt this, but that's not relevant here.) Behe's book is a failure, but his hypothesis stands.

So here we are: an interesting and potentially revolutionary hypothesis has been advanced. It has a certain explanatory appeal, and it has unquestioned relevance for believers of many kinds. It is empirical and rational. And, I maintain, it is testable, at least in principle. And so I'm offering to collaborate on a real effort to test it.

2. Behe's proposal leads to certain types of testable predictions. He claims that the genetic changes that underlie certain levels of evolutionary change occurred non-randomly. In other words, he claims that there is a dramatic mismatch between rates of genetic mutation and rates of evolutionary change. His efforts in EoE were ridiculously inadequate. Here is an outline of an approach that could succeed.

• One major mistake that Behe made was to devote most of his attention to a "case study" in which significant genetic change did not occur. His case study was poorly suited to his purpose, but even if it had been better conceived it would be worthless. We can't learn about how evolution works by analyzing examples in which it didn't occur. (Well, of course it did occur in Behe's case study, but the changes that he claims are non-random are different by his own definition.)
• So, any approach to the detection of non-random influences on evolutionary change needs to focus on case studies that actually involve the relevant level of evolutionary change. Examples should be easy to find, by considering the tree of life and the branching levels at which one would hypothesize non-random change.
• The evolutionary lineage(s) selected for analysis should be fairly well-documented, so that the nature of the relevant common ancestors can be reasonably inferred. This probably means that much deeper lineages (such as eukaryotes or even multicellular eukaryotes) would not make good subjects of analysis. Since Behe is pretty sure that design characterizes differences at the level of class (and deeper), this concern is not a barrier to addressing his hypothesis, at least at those levels of divergence. The tetrapod lineage could serve well, but there are any number of evolutionary trajectories that could be considered.
• Within the selected lineage(s), one or more evolutionary changes would be selected for genetic analysis. Changes could be simple (such as the molecular evolution of a particular protein of interest) or more complex (such as the development of a particular attribute like teeth or feathers or lungs), and could even include the sum total of the genetic changes in a lineage, but must be amenable to genetic description. Most importantly, the evolutionary changes that are analyzed must be associated with the specific design postulate. The goal is to examine the genetic changes underlying an evolutionary transition that Behe would identify as designed.
• Once the genetic changes of interest have been identified, analysis can proceed the way Behe pretended to proceed in EoE: inferred mutational trajectories can be considered in the light of estimated mutation rates and estimated generation numbers. If non-random mutation is clearly necessary for the evolutionary changes in question, it should be apparent that even the simplest mutational paths leading to change are well beyond the explanation of random mutation.

My description makes the undertaking sound straightforward, and in principle it is, but of course such examination of even a relatively simple evolutionary change is a significant and demanding project. Inferring the genetic makeup of the common ancestor is a project all by itself, and constructing postulated mutational pathways is the kind of work that occupies many professional biologists full-time. (Consider the work of Joe Thornton and his group, considered among the best analyses of this kind.) Estimates of generation number will span huge ranges even after the most careful consideration of the variables.

But this is the work that any real scientist and scholar would know has to be done. Behe's hypothesis is completely untested, and only the kind of study that I have outlined can change that. I invite any scholar with interest in undertaking this project to contact me. I would be interested in joining a collaborative effort to test the non-random mutation hypothesis, and I have some significant resources that could be brought to bear on the problem. This is a serious offer, and I would encourage readers to forward it to anyone who might be interested in discussing the details.

Wait...did you say "eldritch?"

It's exciting to live in the era of evolutionary genomics, when new genomes are being published approximately once a week, and the light of genomic analysis is being trained on more and more branches of the tree of life. This week sees the unveiling of the genome of Amphioxus, a primitive vertebrate that has long been known to be a key piece of the puzzle of animal evolution, and the results are sharpening our hypotheses about the genesis of major animal groups.

First a little about the results published in this week's Nature. Amphioxus is the fancy name for lancelets, which are small and simple sea-going creatures that represent a very interesting branch on the tree of life: they constitute a group called the cephalochordates, which is one of the three living groups of chordates. (Remember "kingdom, phylum, class, order, family, genus, species"? Humans are vertebrates, and vertebrates are a subdivision of the chordates.) Vertebrates and tunicates (sea squirts) are the other two groups. Because the lancelets are similar in structure to vertebrates, more so than are the tunicates, they were long thought to be more closely related to vertebrates, and so it was postulated that tunicates were more "basal" on the evolutionary tree. But two years ago, new analyses strongly suggested that it is the lancelets that are the most basal group. And so the lancelets became even more interesting: understanding their genomic structure would surely provide clues to the nature of the original chordate genome.

The examination of the lancelet genome (well, it's the genome of one lancelet of one species) provides substantial new insight into vertebrate evolution. For some solid overviews, check out Nobel Intent at Ars Technica, and the press release from UC Berkeley. Here are just a few tidbits that got my attention:

• The findings strongly support the hypothesis that the vertebrate gene set was diversified through two ancient whole-genome duplications. This phenomenon and its role in the generation of new gene functions have been discussed here before.
• The lancelet genome contains roughly the same number of genes as the human genome.
• Comparison of the various chordate genomes reveals that there are very few chordate-specific genes. Specifically, the authors described 239 "chordate gene novelties" out of 22,000 genes in the lancelet. The nature and function of these genes is intensely interesting, and indeed the authors devote a separate report to issues related to this. But think about it: only 1% of the genes in chordates (vertebrates and all their relatives) are "novel" among genes from all other organisms.
• So if the toolbox isn't all that different between lancelets and lions, despite divergence at least 550 million years ago, then what is different? Anything? As John Timmer notes on Nobel Intent, the authors could find relatively few examples of regulatory DNA sequences that are conserved between lancelets and vertebrates, pointing to the likelihood that changes in regulation of a (mostly) common genetic toolkit is a major factor in evolution of form. (Okay, so that was just a plug for evo-devo. It's my blog.)

But one more thing. Why the bizarre title for this blog entry? Well, Henry Gee at Nature wrote a very nice News & Views summary of the genome report, and here are a few not-so-randomly-selected excerpts:

The age of genomics has rescued the amphioxus from chthonic obscurity, as new data — now including Putnam and colleagues’ paper and three companion reports in Genome Research — have reinvigorated the study of the origin of the vertebrates.

Is there a typo in there?

The 520-megabase genome of B. floridae would, therefore, be nothing much more than a curiosity without the comparative context offered by the increasing number of completed or draft animal genomes from humans to sea anemones... Such studies reveal the amphioxus genome to be, in fact, of preternatural importance.

Uh...

But with Putnam and colleagues’ publication on page 1064 of the draft genome sequence of Branchiostoma floridae, one of the 25 or so recognized species of amphioxus, this eldritch organism is set to re-enter public life.

Eldritch? Eldritch?? What the heck?!

'Preternatural' I can handle, barely, but 'eldritch' and 'chthonic'... Yes, there's a story here, and it's very funny. Enjoy, and have fun in your next Scrabble game.

Finches, bah! What about Darwin's tomatoes?

Charles Darwin collected all sorts of cool stuff (like a vampire bat, caught while feeding on his horse) on his journey aboard the Beagle, and it has to be said that he understood little of it until after he got back. The finches that bear his name were identified as such by someone else, and his own bird collections from the Galapagos were nearly worthless due to the fact that he hadn't bothered to label specimens as to their place of origin. It was only upon their correct identification as different species of finch that Darwin realized that the birds represented what we now call an adaptive radiation.

Darwin collected a lot of plant material, too, and much of it was completely new to science. J.D. Hooker was a botanist and contemporary of Darwin, and in 1851 he wrote a little paper, "An Enumeration of the Plants of the Galapagos Archipelago; with Descriptions of those which are new" describing his studies of Darwin's collection. It was more than 100 pages long.

One unique feature of the collection was a pair of species of tomato plant. Like all other species in the archipelago, the Galapagean tomatoes resemble South American species, but are subtly different. More interestingly, the two Galapagean species are highly similar to each other (and reproductively compatible), but occupy separate habitats and exhibit some odd variations, including a striking divergence in leaf shape.

Image from Figure 1 of Kimura et al., cited below. On the left is S. cheesmaniae; on the right is S. galapagense.

How might such a variation arise in evolution? A nice study published in Current Biology two weeks ago provides the interesting answer, and addresses an important question raised by evo-devo theorists. The article is "Natural Variation in Leaf Morphology Results from Mutation of a Novel KNOX Gene," by Seisuke Kimura and colleagues at UC Davis.

Look again at the picture: the leaves pictured on the left are "normal" tomato leaves, as one might see in a Michigan garden or on the South American plants thought to be the ancestors of the Galapagean species. The leaves on the right are significantly more complex. (For lovers of botanical detail, the "normal" leaves are unipinnately compound, while the S. galapagense leaves are three- or four-pinnately compound. For the botanically challenged like me, the leaves on the right are more snowflake-like.)

This trait has long been known to be under the control of a single gene, but the nature of that gene and its effects were unknown before the experiments of Kimura et al. They did some pretty intense genetic mapping, and zeroed in on a rather small piece of the genome. Specifically, they ended up examining a region 1749 base pairs in length. Inside that region, they found exactly one change that could account for the leaf variation: a deletion of a single base pair. One DNA letter, removed from the genome, makes all that difference.

But there's more. That change isn't in the coding region of a gene, meaning that the mutation doesn't affect the structure of any protein. Like the genetic variation that Cretekos et al. studied in their analysis of bat wing development, this is an example of a change in a regulatory region of the DNA, the kind of change that evo-devo theorists have predicted to be fairly common in the evolution of new forms.

The authors showed that the teeny little one-letter change results in a huge increase in the amount of a protein called TKD1. And they did a compelling experiment similar to the one that Cretekos and colleagues did with the bat and the mouse: they took that piece of regulatory DNA (with the one-letter change) and stuck it into a tomato plant, and showed that it could induce a complex-leaf trait all by itself. No change in protein structures, just a one-letter change in a regulatory DNA region. Isn't that cool?

Kimura et al. went on to show that TKD1 reduces the formation of a complex between two other proteins, and their data suggest that the levels of TKD1 constitute a dimmer switch-like (rheostat) control on that complex, which ultimately controls the development of leaf shape.

Now, here's why this result is interesting in the context of evo-devo. A structural mutation in a protein that controls development can result in dramatic changes in form, for sure. But such a mutation will likely alter all of the processes controlled by that protein, resulting in widespread developmental reorganization. (Think "hopeful monster" here.) Evo-devo thinkers assert that regulatory changes are better suited (in general) for the induction of evolutionary changes in form, because such changes can affect isolated developmental processes without affecting the overall development of the organism. In this case, the excess TDK1 protein is able to inhibit the action of a particular complex in particular areas at particular times, without interfering in the functions of those other proteins elsewhere and at other times. Here are the concluding sentences of the paper:

Mutations affecting the expression levels of transcription factors can modify the function of a major developmental regulatory complex in some organs without interfering with its other essential roles in morphogenesis. Such dosage-sensitive interactions may be broadly responsible for evolutionary change and provide a relatively simple mechanism for the generation of natural variation.

I hope you agree that studies like this one and the bat-wing story are inherently interesting. But I hope you also see how sadly foolish it is to disparage evolutionary science as mere mythology, or to pretend to invalidate a century of evolutionary genetic analysis with a few bogus calculations. Scientists are weird enough to think tomato plant leaves on the Galapagos are worth subjecting to detailed genetic analysis, and maybe that means we're a bit on the obsessive side. But come on: we're not stupid.

Article(s) discussed in this post:

KIMURA, S., KOENIG, D., KANG, J., YOONG, F., SINHA, N. (2008). Natural Variation in Leaf Morphology Results from Mutation of a Novel KNOX Gene. Current Biology, 18(9), 672-677. DOI: 10.1016/j.cub.2008.04.008

How the bat got its wing

Nothing can be more hopeless than to attempt to explain this similarity of pattern in members of the same class, by utility or by the doctrine of final causes. The hopelessness of the attempt has been expressly admitted by Owen in his most interesting work on the 'Nature of Limbs.' On the ordinary view of the independent creation of each being, we can only say that so it is;—that it has so pleased the Creator to construct each animal and plant.

The explanation is manifest on the theory of the natural selection of successive slight modifications,—each modification being profitable in some way to the modified form, but often affecting by correlation of growth other parts of the organisation. In changes of this nature, there will be little or no tendency to modify the original pattern, or to transpose parts. The bones of a limb might be shortened and widened to any extent, and become gradually enveloped in thick membrane, so as to serve as a fin; or a webbed foot might have all its bones, or certain bones, lengthened to any extent, and the membrane connecting them increased to any extent, so as to serve as a wing: yet in all this great amount of modification there will be no tendency to alter the framework of bones or the relative connexion of the several parts.

– from On the Origin of Species, 1st Edition (1859), Charles Darwin

The wing of a bat is an amazing thing. It's not just a wing; it's clearly a modified mammalian limb. A bat looks like a lot like a rodent with really long, webbed fingers on elongated arms.

Image from Animal Diversity Web at the University of Michigan.

Recent genetic analyses have yielded a fairly solid outline of the evolutionary history of bats, which have left a somewhat poor fossil record in which the earliest fossil bats look pretty much like modern bats. It seems that bats arose relatively quickly during evolution, acquiring their distinctive feature – powered flight – in a few million years. No transitional forms have yet been found, which is a shame, because this particular evolutionary transition is the kind that is otherwise reasonably approachable for the detailed study of how changes in form come about.

The fossils can't yet show us how paws gave rise to wings, but that doesn't mean we can't test specific hypotheses regarding the paths that evolution could have taken. In fact, developmental biologists have enormous resources that can be brought to bear on the question, by virtue of decades of research on the development and genetics of the wingless terrestrial bat better known as the mouse. A few months ago, an interesting new report described one kind of genetic change that can lead to bat-like bodies, and the findings put some new wind in the sails of evo-devo.

Two of the more remarkable aspects of bat wing structure are the forelimbs and the forelimb digits, what humans would call the arms and the fingers. Both are dramatically elongated in the adult animal, despite getting off to a very typical start during early development. Check it out: in the picture below, bat and mouse limbs are compared with the image scaled so that body lengths are comparable.

Image from Figure 1 of Cretekos et al., cited below.

Developmental biologists have some pretty good ideas about how this might arise physiologically: certain growth factors (called bone morphogenetic proteins, or BMPs) are known to control limb growth, and some BMPs seem to be turned up in developing bat fingers. But the genetic mechanisms underlying these processes are unknown.

Enter Chris Cretekos and colleagues, then working in a group in Houston headed by Richard Behringer. They set out to examine the genetic underpinnings of the elongation of the forelimbs (arms) of bats, using the formidable tools of mouse developmental genetics. And, clearly, they also sought to directly test one of the central hypotheses of evo-devo: that changes in regulatory DNA sequences (as opposed to changes within the genes themselves) are a potent source of variation in evolution. Consider the beginning of their abstract:

Natural selection acts on variation within populations, resulting in modified organ morphology, physiology, and ultimately the formation of new species. Although variation in orthologous proteins can contribute to these modifications, differences in DNA sequences regulating gene expression may be a primary source of variation.

– From C.J. Cretekos et al., "Regulatory divergence modifies limb length between mammals, Genes & Development 22:141-151, 15 Jan. 2008

Besides their expertise in mouse genetics, the authors brought two major assets to their study: 1) they had already carefully mapped the development of the short-tailed fruit bat (Carollia perspicillata, "our model Chiropteran"); and 2) they knew a lot about the genetic control of limb length in other mammals. In particular, they knew that the protein Prx1 is known to influence limb elongation, by controlling the expression of other genes. So they hypothesized that changes in the activity or level of Prx1 might underlie the difference in limb length between bats and mice, and they were well-equipped to do the experiments.

First, the authors examined the Prx1 gene in the two species, and found that the overall structure of the gene is very similar in both mice and bats, and that the actual coding sequences of the two genes are almost completely identical. (Aligning the coding sequences showed that more than 99% of the amino acids are the same in both species.) In other words, the part of the Prx1 gene that codes for protein is almost certainly not a source of variation between mice and bats. This could mean that Prx1 doesn't have anything to do with the difference between forelimb length in these two species, or it could mean the the difference is generated, at least in part, by variation in the regulation of the gene. Cretekos et al. postulated that altered Prx1 regulation might be involved, and designed a cool experiment to address this possibility.

They already knew that the Prx1 gene in mice contains known regulatory elements in particular locations within the gene. (Such elements are often located in the DNA sequences that precede the coding region.) When they looked at the bat gene, they found similar elements in the same location, but these elements showed some intriguing variation: when the two regions were aligned, they shared only 67% identity, meaning that a third of the DNA bases were different in mouse and bat. They did some nifty cell biology to show that this region did function as a regulator of the expression of Prx1, then did something that biologists could only dream about before the genomic era: they altered the mouse genome by replacing the mouse regulatory region with the corresponding region from the bat genome. In other words, they gave a mouse a piece of a bat's genome, without actually changing the coding sequence of any gene.

The result was dramatic, although it won't sound that way at first. The mice with the bat DNA displayed forelimbs that were 6% longer than normal. Why is this a dramatic result? Well, first of all, think about a 6% change in a major structural attribute. If adult males in a certain country average 5'10" in height, a 6% increase would mean an increase of more than 4 inches. But more importantly, the Prx1 gene is known to account for about 12% of forelimb length – mice that lack the gene altogether show a 12% reduction in forelimb length. That 6% change reflects a huge change in Prx1 activity, a change that was completely due to alterations in regulatory DNA sequences without any change in coding sequence.

If that's not impressive enough, the authors went on to examine the importance of this regulatory region in mice, by deleting it altogether. The result was very surprising, but very interesting: limb length in mice was completely unaffected by the loss of this chunk of regulatory DNA. (The region we're discussing is 1000 bases in length.) This means that the Prx1 gene of both bats and mice contains a regulatory region that is completely dispensable for normal development but that can be altered to generate significant changes in limb length, which points to significant evolutionary potential in genetic regions that seem unimportant. Here's how the authors say it:

Maintenance of redundant enhancers for essential developmental control genes would allow changes in expression pattern to arise from mutations that alter regulatory activity while preserving the required gene function.

So, why is this significant? Here are two aspects of the story that are worth highlighting.

1. The results provide strong (and rare) experimental support for the ideas of the evo-devo school. The currently-heated debate over the merits of evo-devo is focused on the central evo-devo claim that morphological evolution (i.e., evolutionary changes in form) is driven to a large extent by changes in the regulation of gene expression, and less so by changes in the structures of the proteins that are encoded. To simplify, evo-devo postulates that significant evolutionary change – like that discussed here – is more likely a result of the varied use of a protein toolkit than a result of modification of the toolkit itself. Cretekos et al. have presented a case in point, and one that is considered outstanding in that it documents a morphological gain; many previous examples showed only losses.

2. The results provide a sharp picture of what Darwin's vision of "successive slight modifications" means in terms of developmental biology. In this case, the modifications (of a redundant regulatory region) can yield significant anatomical remodeling without altering protein structure at all.

The article was a notable advance for evo-devo and for evolutionary science, but soon there will surely be many others like it. Desperate or ignorant creationists will always find a way to avoid facing the explanatory power of common descent, but scientists are just plugging away, and for every blog post by a creationist ignoramus, there are 30 unheralded publications in the biological literature that advance our understanding of common descent and the mechanisms that generate biological novelty. And they're fun to read.

Article(s) discussed in this post: Cretekos, C.J. et al. (2008) Regulatory divergence modifies limb length between mammals. Genes & Development 22:141-151.