22 May 2008

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 ResearchBlogging.orgspecimens 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

17 May 2008

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. ResearchBlogging.orgIt 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:

15 May 2008

Weekly sampler 18

1. A nice new Tangled Bank went up yesterday at The Beagle Project Blog, which is a cool site worth visiting at other times, too.

2. Last week saw the unveiling of the Evangelical Manifesto, "an open declaration of who Evangelicals are and what they stand for," which seeks "to rally and to call for reform." The document has sparked some pretty intense discussion among Christians I know. Some of my colleagues at Calvin have denounced it fairly strongly, at least in part due to frustration with evangelical politics. Jamie Smith (another Calvin colleague) has some interesting remarks in three parts (II and III) at Generous Orthodoxy Think Tank, and profitable discussion ensued. Here's one excerpt of clear relevance here:
All too often we have disobeyed the great command to love the Lord our God with our hearts, souls, strength, and minds, and have fallen into an unbecoming anti-intellectualism that is a dire cultural handicap as well as a sin. In particular, some among us have betrayed the strong Christian tradition of a high view of science, epitomized in the very matrix of ideas that gave birth to modern science, and made themselves vulnerable to caricatures of the false hostility between science and faith. By doing so, we have unwittingly given comfort to the unbridled scientism and naturalism that are so rampant in our culture today.
All well and good, but it's the last sentence I don't like. It's certainly true that evangelical credulity and ignorance are potent fuels for New Atheist engines, but in my opinion that's not the primary danger of the malignancy of obscurantism. Evangelical buffoonery on scientific matters betrays a deep and latent gnostic infection – North American evangelicals, in my experience, too frequently veer right to the brink of outright Gnostic heresy. "False hostility between science and faith," it seems to me, is actually real hostility toward the natural world, as evidenced by a pervasive preference for supernatural action as "God's work." I would have written something very different at the end of that paragraph – something sort of like this:
By doing so, we have unwittingly given comfort to the unbridled gnosticism that is so rampant in Christendom today, a great and ancient heresy that cleaves the creation in two, inviting the open degradation of God's good work by those who mistakenly assume that what is natural or material is worthless.
But I do like the document overall, and I agree with one commenter at the Generous Orthodoxy Think Tank who pointed out that it's the discussion of the document that makes it come alive.

3. I'm currently engaged with a discussion on the ASA listserv with one pseudonymous Mike Gene. He's recently published a book, and blogs at a site promoting that book. But wait...he's one design proponent who seems to be swimming clear of the Discovery Institute wreckage, by virtue of uncharacteristic intelligence and intellectual integrity. It's still ID, and I'm not enthused about the pseudonymity, but if you're looking for a pro-ID thinker who actually acts like an adult, Mike Gene is someone to check out. James McGrath gives the book a strongly positive review over at Exploring Our Matrix.

4. ORFans are genes that seem to exist in isolation, say in one or only a few closely-related species. They seem to have just popped into existence in those species, amid a huge common collection of genes shared by, say, all animals. If this sounds weird or interesting to you, go to Panda's Thumb to learn more. (Yes, of course, ID fellows have seized on this as another piece of ignorance on which to build.)

5. Check out someone's illustrated list of the world's 25 weirdest animals. I'm pretty sure I saw Dobby in there.

6. Gordon Glover is continuing his excellent series on science & Christian education. What do the Antipodes have to do with evolution? Are they anywhere near the Antilles or the Galapagos? Well, I'm not going to tell you; Gordon does it better.

7. Publishers Weekly online has a little interview with Ken Miller. He mentions his part in the intriguing new Templeton effort in which they've gotten a collection of big-brained white men (and one woman) to address the question "Does science make belief in God obsolete?" Included is a debate between Miller and Christopher Hitchens.

8. On the ASA web site, Jeffrey Schloss of Westmont College has an extensive review essay on Expelled, "The Expelled Controversy: Overcoming or Raising Walls of Division?" A blog was set up to allow discussion among ASA members (I'm not a member, dang it); not much there yet, but maybe that will change soon.

11 May 2008

Weekly sampler 17

It'll be a breakout week after a slow month on the blog. To the Edge of Evolution – and beyond!

1. Ian Musgrave over at Panda's Thumb provides a nice summary of the evolution of clotting systems and some new genomic data that could be used, by ID proponents like Michael Behe, to bolster their claims regarding the "irreducible complexity" of the clotting system. I've been saying it since the beginning here at QoD: genomic data has already made it nearly impossible to respectably doubt common descent, and it gets much worse every day.

2. Massimo Pigliucci gibbers on the Problem of Evil and Francisco Ayala. Not that I'm buying Ayala's theodicy either...

3. Dale Purves is an eminent neuroscientist whose work I've followed for two decades. In the last several years, he's expanded from developmental neurobiology into cognitive neuroscience. His lab's web page is loaded with good stuff, which is probably why it was recently honored by The Scientist. The resources page includes a bunch of interesting illusions and the full text of two of his out-of-print books.
Ebola virus, electron micrograph. Image from PHIL, ID# 1835.

4. The CDC (Centers for Disease Control & Prevention) has a free online image library called PHIL (Public Health Image Library). Now you know where to go to get your pictures of Ebola Virus for when you make your own Get Well Soon cards. Don't miss this little disclaimer:
WARNING: This library includes subject matter that might be unsuitable for children. Viewing discretion is advised.

5. Get to Gordon Glover's Beyond the Firmament blog for a superb series on "Science and Education" focused on questions surrounding natural science (mostly origins) and Christian education. He's covering folk science right now, in his excellent style. And you don't even have to pay.

6. Last week saw the unveiling of the platypus genome, and it included lots of interesting surprises. The media coverage has been typically spotty (with regard to accuracy); to get well-grounded, start with the brief piece at the New York Times then check out Ryan Gregory's thoughts (at his new blogging home) and perhaps the usual clarity dispensed by the cuddly PZ Myers.

02 May 2008

Weekly sampler 16

Well, no sampler last week, so here are the answers to the last DNA content quiz.
  • Top row: the beluga whale has a slightly larger genome than the brine shrimp (3.29 vs. 2.91).
  • Second row: the damselfly, in all its beauty and intricacy, sports a genome half the size of that of the woodlouse hunter (1.50 vs. 3.00).
  • Third row: the aardvark needs more than twice as much DNA as the American cockroach (5.87 vs. 2.72). Ah, now that must be due to "degree of advancement." Just what a well-conceived biblical creation model would have predicted. NOT.
  • Bottom row: the chameleon's genome is almost 10 times the size of the leech's (2.24 vs. 0.23). Another victory for junk science!
Just don't speak of the mountain grasshopper (16.93) and the bald eagle (1.43).

So, what's been keeping me so busy that I can't attend to my blog?

1. I've made a lot of dumb decisions in my time, but one magnificent success covers for all of them: a quarter of a century ago, I somehow convinced Susan Massee to enter into a long-term collaboration which has been enormously fruitful. We have four great kids (two teenagers, one of whom has a blog of her own) and lots of stories, but only recently have we started collaborating professionally. We'll be teaching two classes together in the next several months, with the most exciting one taking us (we hope) to London and Edinburgh next January. The idea is to explore the Christian roots of the Scottish Enlightenment, with Harry Potter as a theme (you know, to get us in the mood), and superstars like Hume, Reid, Burns and Smith as favored ghosts. It'll be a blast; now we just need to get about 20 students to sign up. We've been working on promotion and planning, trying not to emphasize Scotland's January climate. (Which, of course, is a heck of a lot better than Michigan's.)

2. Susan did change her name (it was a long time ago), so you'll need to add my Scottish surname to hers when looking for her work online. Start at the fascinating online magazine Catapult, then check out Calvin's television program, Inner Compass.

3. John Farrell passes along an interesting take on Michael Behe and his weird new book that I've been discussing here; see Laelaps for discussion of Behe's curious absence from a recent propaganda film. Key point: the Discovery Institute seems unenthused by the book, probably because Behe gave away the store. Here's Richard Dawkins in his review in the New York Times:
Behe correctly dissects the Darwinian theory into three parts: descent with modification, natural selection and mutation. Descent with modification gives him no problems, nor does natural selection. They are “trivial” and “modest” notions, respectively. Do his creationist fans know that Behe accepts as “trivial” the fact that we are African apes, cousins of monkeys, descended from fish?
Well, heh, maybe now they do.

4. Sorry I'm late on this, but a week and half ago D.W. Congdon at The Fire and the Rose presented Four theses against Intelligent Design. Please check it out. I'm particularly interested in his comments on natural theology and his blunt equation of ID with a "god of the gaps." My friend and colleague Del Ratzsch has convinced me that design arguments need not evoke god-of-the-gaps fallacies, but I find the ID movement to be rife with that malignancy, and Congdon's harsh judgment of such errors is spot-on. When I comment further on Behe's The Edge of Evolution, I'll claim that the book is nothing more than a single, flawed, ignorance-based argument, with the desperate aim of creating a gap.

5. I recently heard Stephen H. Webb, American Theologian, give a talk and thereafter concluded that his web site is not the parody I initially took it to be. I won't say much about the talk, for various reasons. But after hearing him speak, and looking at some of his other writing, I was unsurprised to see that he wrote a comically uninformed positive review of The Edge of Evolution. The comments reveal that not all of the readers of Christianity Today are as gullible as Stephen H. Webb, American Theologian. That's encouraging, eh?

6. John Derbyshire is a columnist at National Review, which makes him a conservative. (I used to refer to myself in that way, but I really don't know what it means anymore.) You thought I can't stand ID? Check out his remarkable condemnation of the movement, Henry V-like in its merciless passion. The high point:

And now here is Ben Stein, sneering and scoffing at Darwin, a man who spent decades observing and pondering the natural world — that world Stein glimpses through the window of his automobile now and then, when he’s not chattering into his cell phone. Stein claims to be doing it in the name of an alternative theory of the origin of species: Yet no such alternative theory has ever been presented, nor is one presented in the movie, nor even hinted at. There is only a gaggle of fools and fraudsters, gaping and pointing like Apaches on seeing their first locomotive: “Look! It moves! There must be a ghost inside making it move!”

The “intelligent design” hoax is not merely non-science, nor even merely anti-science; it is anti-civilization. It is an appeal to barbarism, to the sensibilities of those Apaches, made by people who lack the imaginative power to know the horrors of true barbarism. (A thing that cannot be said of Darwin. See Chapter X of Voyage of the Beagle.)

I don't know what Derbyshire has against Apaches, but that's beside the point.

7. I've mentioned Francisco Ayala before: he's a real evolutionary biologist, the kind who performs research and co-authors scientific papers as opposed to the kind who keeps a blog or leads a religious crusade. Read about him and his new book at the New York Times, and let me know your thoughts on the book, which I'll read and review sometime in the next...year. :-)