30 October 2007

PZ's mutating meme

About a week and a half ago, I was infected with an evolving blog meme, and I think the only way to get better is to pass it on. Brian over at Laelaps tagged me; maybe he's annoyed about my suggestion to his profs that they assign him more homework, or maybe he's indignant at my mention of the RU Screw. I know he wants to be a transitional fossil, but I doubt he wants to be an evolutionary dead-end, so I'll help him out just this once.

The meme started over at Pharyngula, where you can read about its origins. Here are the rules:

There are a set of questions below that are all of the form, "The best [subgenre] [medium] in [genre] is...". Copy the questions, and before answering them, you may modify them in a limited way, carrying out no more than two of these operations:
* You can leave them exactly as is.
* You can delete any one question.
* You can mutate either the genre, medium, or subgenre of any one question. For instance, you could change "The best time travel novel in SF/Fantasy is..." to "The best time travel novel in Westerns is...", or "The best time travel movie in SF/Fantasy is...", or "The best romance novel in SF/Fantasy is...".
* You can add a completely new question of your choice to the end of the list, as long as it is still in the form "The best [subgenre] [medium] in [genre] is...".
* You must have at least one question in your set, or you've gone extinct, and you must be able to answer it yourself, or you're not viable.
Then answer your possibly mutant set of questions. Please do include a link back to the blog you got them from, to simplify tracing the ancestry, and include these instructions.
Finally, pass it along to any number of your fellow bloggers. Remember, though, your success as a Darwinian replicator is going to be measured by the propagation of your variants, which is
going to be a function of both the interest your well-honed questions generate and the number of successful attempts at reproducing them.

First, my phylogeny:
My great-great-great-grandparent is Metamagician and the Hellfire Club.
My great-great-grandparent is Flying Trilobite
My great-grandparent is A Blog Around the Clock
My grandparent is The Anterior Commissure
My parent is Laelaps

And my contributions to the meme pool:

The best scary movie in sociopolitical dystopias is:
Children of Men

The best sexy song in pop rock is:
"With or Without You" by U2.

The best scary story in romantic short stories is:
"The Cask of Amontillado" by Edgar Allan Poe

The best B-movie in 1980's horror films is:
I'm leaving this one in, but I've never seen this fine piece of cinematic art, or any other B-movie in the horror genre, and I've already used up my two mutations. I think this is a blow to my viability, but we'll let God PZ decide.

Now I get to infect some other bloggers. I'd like to infect ERV, but she's already been kissed, and she's a busy grad student, so I'm going to target Christians for infection. I tag:
John Farrell
Steve Martin at An Evangelical Dialogue on Evolution
The Fire and the Rose

Now we'll see whether this expansion into a new niche will result in an adaptive radiation or a mass extinction.

29 October 2007

Blogging on peer-reviewed research

One of my main goals in this blog is to help non-scientists (Christian readers in particular) understand science and God's world, by reviewing and explaining recently-published scientific research. I've been calling these posts "Journal Clubs" in honor of the kind of small-group discussion of the literature that formed the backbone of my scientific education (past and present).

It takes a lot more effort to prepare one of those articles than it does to post a link to the latest gaffe by a creationist or a racist Nobel laureate, and I've often wished I could make my Journal Club entries stand out more. It turns out, not surprisingly, that plenty of other science bloggers (and/or blogging scientists) have had the same desire. Happily, some of them actually did something about it, resulting in the creation of Bloggers for Peer-Reviewed Research Reporting, now incarnated at BPR3.org.

You can read all about it on Cognitive Daily over at ScienceBlogs; one of the bloggers there, Dave Munger, is spearheading the BPR3 effort.

So, I'm joining this excellent movement. From now on, I'll mark my Journal Clubs with the official icon. This will enable readers to identify the serious science, and the posts will find their way into a collection at BPR3 through an aggregator. Just as importantly, I think, the icon commits me to a set of standards, which includes:

  1. The post should offer a complete formal citation of the work(s) being discussed.
  2. The post author should have read and understood the entire work cited.
  3. The blog post should report accurately and thoughtfully on the research it presents.
  4. Where possible, the post should link to the original source and / or provide a DOI or other universal reference number.
  5. The post should contain original work by the post author -- while some quoting of others is acceptable, the majority of the post should be the author's own work.
And this is cool and important: abuse can be reported, and repeated misconduct gets your work kicked out of the aggregator. Nice.

So look for the just-unveiled icon of BPR3 on my Journal Club articles henceforth, and thanks for shopping at Quintessence of Dust.

An example of purely naturalistic explanation

2004 might have been a miracle, but...

24 October 2007

They selected teosinte...and got corn. Excellent!

Evolutionary science is so much bigger, so much deeper, so much more interesting than its opponents (understandably) will admit. It's more complicated than Michael Behe or Bill Dembski let on, and yet it's not that hard to follow, for those who are willing to try. The best papers by evolutionary biologists are endlessly fascinating and scientifically superb, and reading them is stimulating and fun.

Yet, as an experimental developmental biologist reading work in evolutionary biology, I often find myself yearning for what we call "the definitive experiment." Molecular biology, for example, can point to a few definitive experiments -- elegant and often simple -- that provided answers to big questions. Sometimes, while examining an excellent evolutionary explanation, I think, "Wouldn't it be great if they could do the experiment?"

Now of course, plenty of evolutionary biology is experimental, and I've reviewed some very good examples of experimental evolutionary science on this blog. But when it comes to selection and the evolution of new structures and functions, the analysis often seems to beg for an experiment, one that is simple to conceive but, typically, impossible to actually pull off -- there's not enough time. The previous Journal Club looked at one way around this limitation: bring the past back to life. Even better, though, would be to find an example of evolutionary change in which the new and old forms are still living, so that one could do the before-and-after comparison. It would look something like this: take a species, subject it to evolutionary influences of some kind until the descendants look significantly different from the ancestors, then compare the genomes (or developmental processes) of the descendant and the ancestor, in hopes of discovering the types of changes at the genetic or developmental level that gave rise to the differences in appearance or function of the organisms. That would be a cool experiment.

In fact, that kind of experiment has been done, more than once. The best example, in my opinion, involves an organism far less sexy than a dinosaur or a finch or a whale: Zea mays, better known as corn (or maize).

Corn is a grass, but a grass that's been so extensively modified genetically that it's barely recognizable (to non-specialists like me) as a member of that family. Wait...genetically modified? Yes, and I'm not talking about the really modern tricks that gave us Bt corn or Roundup Ready corn. In fact, the wonderful stuff they grow in Iowa is quite different from the plants that humans first started to harvest and domesticate in Central America a few millenia ago. Corn as we know it is the result of a major evolutionary transformation, driven by selection at the hands of humans. (I don't find the natural/artificial selection distinction at all useful, since there's no explanatory difference, but you can refer to the selection under consideration here as 'artificial' if it makes you feel better.) The story has been a major topic in evolutionary genetics for decades, but it's largely absent from popular discussions, probably because the Discovery Institute has wisely avoided it. I hope it will soon be clear why you won't find the word 'teosinte' anywhere at discovery.org.

For many years, the origin of corn was a mystery. Like most known crops, it was domesticated 6000-10,000 years ago. But unlike other crops, its wild ancestor was unknown until relatively recently. Why this odd gap in our knowledge? Well, it turns out that corn is shockingly different -- in form, or morphology -- from its closest wild relative, which is a grass called teosinte, still native to southwestern Mexico. In fact, corn and teosinte are so different in appearance that biologists initially considered teosinte to be more closely related to rice than to corn, and even when evidence began to suggest a genetic and evolutionary relationship, the idea was hard to accept. As John Doebley, University of Wisconsin geneticist and expert on corn genetics and evolution, puts it: "The stunning morphological differences between the ears of maize and teosinte seemed to exclude the possibility that teosinte could be the progenitor of maize." (From 2004 Annual Review article, available on the lab website and cited below.)

But it is now clear that teosinte (Balsas teosinte, to be specific) is the direct ancestor of corn. In addition to archaeological evidence, consider:

  • The chromosomes of corn and teosinte are nearly indistinguishable at very fine levels of structural detail.
  • Analysis using microsatellite DNA (repetitive DNA elements found in most genomes) identified teosinte as the immediate ancestor of corn, and indicated that the divergence occurred 9000 years ago, in agreement with archaeological findings.
  • Most importantly, a cross between corn and teosinte yields healthy, fertile offspring. So, amazingly, despite being so different in appearance that biologists initially considered them unrelated, corn and teosinte are clearly members of the same species.
The basic idea, then, is that corn is a domesticated form of teosinte, exhibiting a strikingly distinct form as a result of selection by human farmers. And that means that we have a perfect opportunity to examine the genetic and developmental changes that underlie these "stunning morphological differences." We can do the experiment.

First, have a look at an example of one of the evolutionary changes in teosinte under human selection.

The small ear of corn on the left is a "primitive" ear; the brown thing on the right is an ear from pure teosinte. (Both are about 5 cm long.) The "primitive" ear is similar to archaeological specimens representing the earliest known corn. Image from John Doebley, "The genetics of maize evolution," Annual Review of Genetics 38:37-59, 2004. Article downloaded from Doebley lab website.

The thing on the far left is a teosinte "ear," the far right is our friend corn, and the middle is what you get in a hybrid between the two. Photo by John Doebley; image from Doebley lab website.

The pattern of branching of the overall plant is also strikingly different between corn and teosinte, and you can read much more on the Doebley lab website and in their publications.

When I first heard about this work at the 2006 Annual Meeting of the Society for Developmental Biology, I was astonished at the amount of basic evolutionary biology that was exposed to experimental analysis in this great ongoing experiment. Here are two key examples of the insights and discoveries generated in recent studies of corn evolution.

1. Does the evolution of new features require new, rare, mutations in major genes?

Perhaps this seems like a stupid question to you. Anti-evolution propagandists are eager to create the impression that evolutionary change only occurs when small numbers of wildly improbable mutations somehow manage to help and not hurt a species. And in fact, experimental biology has produced good examples of just such phenomena. But there is at least one other genetic model that has been put forth to explain the evolution of new forms. This view postulates that many major features exhibited by organisms are "threshold" traits, meaning that they are determined by many converging influences which add together and -- once the level of influence exceeds a threshold -- generate the trait. The model predicts that certain invariant (i.e., never-changing) traits would nevertheless exhibit significant genetic variation, since evolutionary selection is acting on the overall trait and not on the individual genetic influences that are added together. Hence the implication that...
...populations contain substantial cryptic genetic variation, which, if reconfigured, could produce a discrete shift in morphology and thereby a novel phenotype. Thus, evolution would not be dependent on rare mutations, but on standing, albeit cryptic, genetic variation.
--from Nick Lauter and John Doebley, "Genetic Variation for Phenotypically Invariant Traits Detected in Teosinte: Implications for the Evolution of Novel Forms," Genetics 160:333-342, 2002.
In that paper, the authors show that several invariant traits (e.g., number of branches at the flower) in teosinte display significant genetic variation. In other words, the traits are the same in every plant, but the genes that generate the traits vary. The variation is 'cryptic' because it's not apparent in basic genetic crosses. But it's there. The authors ask: "How can cryptic genetic variation such as we have detected in teosinte contribute to the evolution of discrete traits?" Two ways: 1) the variation is available to modify or stabilize the effects of large-effect mutations; and 2) variation in multiple genes can be reconfigured such that it adds up to a new threshold effect. Note that the first scenario is clearly applicable to the kind of evolutionary trajectory outlined by Joe Thornton's group and discussed in a previous post. The second scenario is particularly interesting, however, since it addresses an important question about the role of selection. Consider the authors' discussion of this issue:
At first glance, cryptic variation would seem inaccessible to the force of selection since it has no effect on the phenotype. However, if discrete traits are threshold traits, then one can imagine ... that variation ... could be reconfigured such that an individual or population would rise above the threshold and thereby switch the trajectory of development so that a discrete adult phenotype is produced. We find this an attractive model since evolution would not be constrained to “wait” for new major mutations to arise in populations. (Italics are mine; ellipses denote deletion of technical jargon, with apologies to the authors.)
In fact, in a 2004 review article, Doebley is bluntly critical of the assumption that new mutations were required during the evolution of corn, and seems to suggest that this view led researchers significantly astray:
There is an underlying assumption in much of the literature on maize evolution that new mutations were central to the morphological evolution of maize. The word "mutation" is used repeatedly to describe the gene changes involved, and Beadle led an expedition ("mutation hunt") to find these rare alleles. The opposing view, that naturally occurring standing variation in teosinte populations could provide sufficient raw material for maize evolution, was stated clearly for the first time by Iltis in 1983. Although new mutation is likely to have made a contribution, anyone who has worked with teosinte would agree that teosinte populations possess abundant genetic variation. [...] Allowing for cryptic variants and novel phenotypes from new epistatic combinations to arise during domestication, it is easy to imagine that maize was domesticated from teosinte.
--John Doebley, "The genetics of maize evolution." Annual Review of Genetics 38:37-59, 2004.
Compare that discussion, and others like it in the paper I'm quoting, with the yapping about mutations that passes for anti-evolution criticism of evolutionary genetics. I can find no evidence that Michael Behe or any other ID theorist has even attempted to seriously address the importance of genetic variation in populations. I haven't read The Edge of Evolution yet, but I have it right here, and the index suggests that Behe hasn't tried to engage genetics beyond the high school level. There's a good reason why Behe is an object of scorn in evolutionary biology. He wants you to think it's because his critics are mean. No; it's much worse than that.

2. Does evolutionary change ever result from a "gain of information," or does Darwinian evolution merely prune things out?

It would be easy to get the impression from various creationists and ID proponents that mutation and selection can only remove things from a genome. Young-earth creationist commentary on "microevolution" (a yucky term for the now-undeniable fact of genetic change over time) always adds that this kind of change involves NO NEW INFORMATION. (The caps are important, apparently, since caps and/or italics are de rigueur in creationist denialism on this topic.)

Similarly, Michael Behe wants you to think that beneficial (or adaptive) mutations are some kind of near impossibility, and that when they do happen it's almost always because something's been deleted or damaged, with a beneficial outcome.

Studies of evolution in corn and teosinte (and other domesticated plants), not to mention findings like the HIV story on Abbie Smith's now-famous blog, tell a different -- and, of course, more wonderfully interesting -- story. In a minireview on the genetics of crop plant evolution in Science last June, John Doebley notes that most of the mutations that led to major evolutionary innovations occurred in transcription factors, which are proteins that turn other genes on and off. Then this:
Another remarkable feature of this list is that the domesticated alleles of all six genes are functional. If domestication involved the crippling of precisely tuned wild species, one might have expected domestication genes to have null or loss-of-function alleles. Rather, domestication has involved a mix of changes in protein function and gene expression.
In other words, the new genes are not dead or damaged; they're genes that are making proteins with new functions. ('Allele' is just the term for a particular version of a particular gene, and 'null', as you might have guessed, is a version that is utterly functionless, as though the gene were deleted entirely.) Now, if you've even flipped through The Origin of Species, you might not be surprised by Doebley's conclusion:
Given that the cultivated allele of not one of these six domestication genes is a null, a more appropriate model than "crippling" seems to be adaptation to a novel ecological niche -- the cultivated field. Tinkering and not disassembling is the order of the day in domestication as in natural evolution, and Darwin's use of domestication as a proxy for evolution under natural selection was, not surprisingly, right on the mark.
The change from teosinte to corn happened in about a thousand years. That's fast evolution. Apply selection to a varying population, and you get new functions, new proteins, new genes, completely new organisms. Fast.

So in summary, we can do the experiment. And we've done the experiment. ('We' being John Doebley and his many able colleagues.) And we've learned a lot about evolution and development. Now if we can just get people to read it. Then they'll know more about evolution, and about God's world, and about the trustworthiness of the anti-evolution propaganda machines that are exploiting the credulity of evangelical Christians.

17 October 2007

Pop quiz! Put your browsers away.

UPDATE: answers posted at the end.

Which of these plant specimens doesn't belong? (Images will be properly credited in a forthcoming article which will explain why they're so interesting.)

The images are all the same magnification, but have been colorized so that the color won't give you any clues. Focus on the structure of each specimen, and pick one that doesn't belong with the others. (Insert Sesame Street reference here.)

Want a hint? One word: teosinte (tay-oh-SIN-tay).

ANSWER: Picture number 1 is wheat. The rest are Zea mays. See next post.

15 October 2007

How to evolve a new protein in (about) 8 easy steps

ResearchBlogging.orgIf you have only read the more superficial descriptions of intelligent design theory, and specifically the descriptions of irreducible complexity, you might (reasonably) conclude that Michael Behe and other devotees of ID have claimed that any precise interaction between two biological components (two parts of a flagellum, two enzymes in the blood clotting cascade, or a hormone and its receptor) cannot arise through standard Darwinian evolution. (If you don't know anything about the term 'irreducible complexity' you should probably read a little about it before proceeding.) In other words, you may be under the impression that Behe doesn't think that such a system could arise through a stepwise process of mutation and selection. You may even be under the impression that Behe has demonstrated the near impossibility of such a system coming to be through naturalistic means.

This article was UPDATED on 1 November 2007, incorporating some corrections and clarifications provided by the senior author of the studies described. In other words, this post was peer reviewed, and this is the final version.

You would be mistaken, albeit (in my opinion) understandably so. Behe has not claimed this -- though he's often come pretty close -- and recently he has made it clear that this is not his position. Unfortunately, many of the critiques of irreducible complexity contain significant errors, including the claim that Behe rejects all stepwise accounts of molecular evolution, and you have to look pretty hard to find well-reasoned examinations of the problems with Behe's interesting but fruitless challenge to evolutionary theory.

My purpose in the preamble above is to make it clear that this Journal Club is not intended to refute Behe's claims regarding the ability of Darwinian mechanisms to generate irreducibly complex structures. (In my view, his claims are wholly mistaken, and Christian enthusiasm for his natural theology is a disastrous mistake. But that's for another time.) Rather, it is to discuss a superb recent example of the kind of experimental molecular analysis of evolution that can be done in this postgenomic era. Experiments like this are revealing how evolutionary adaptation actually comes about at the molecular level, thereby addressing the very questions raised by ID thinkers. ID apologists are, in a sense, wise to attack the work described here, because these experiments are the first fruits of the types of analysis that will usher ID into permanent scientific ignominy.

So, to our two papers.

How, exactly, does a protein acquire a new function during evolution? This is one of those "big questions" in evolutionary biology. Broad concepts such as gene duplication are quite helpful in formulating explanations, but the specific question raised is focused on the details -- the actual steps -- that must occur during the step-by-step modification of a protein such that it performs a different job than the proteins from which it has descended. The constraints on the process of change are significant, and the issues are similar to those I discussed when describing the concept of fitness landscapes in morphospace. The problem, basically, is this: how can you change a protein without wrecking it in the process? In other words, can you get from function A to function B, step by step, without passing through an intermediate form, call it protein C, which is worthless (or even harmful)?

These are precisely the questions addressed in an elegant set of experiments reported in two reports over the last year or so. The second article, by Ortlund et al., was reported in the 14 September issue of Science, and built on work reported in Science in April 2006. Their studies focused on two closely-related proteins that are receptors for steroid hormones. In this case, the steroids of interest are corticosteroids (the kind often used to treat inflammation; Ortlund et al. studied receptors for cortisol, which is of course quite similar to cortisone) and a mineralocorticoid (a less well-known hormone, aldosterone, that regulates fluid and salt intake). The hormones are structurally similar (being steroids).

Joseph Thornton, at the University of Oregon, has been studying the origins of these receptors for about 10 years, and has assembled an interesting (and detailed) account of their history. The basic outline is as follows: the original steroid receptor was an estrogen receptor, and is extremely ancient, apparently arising "before the origin of bilaterally symmetric animals" (Thornton et al., Science 2003). (That's seriously ancient, sometime in the Cambrian or earlier.) The progesterone receptor seems to have arisen next, followed by the androgen (i.e., testosterone) receptor. (Now that's intriguing.) Fairly late in this game, the two receptors of interest to us here, the corticosteroid receptor and the mineralocorticoid receptor, were added to the vertebrate repertoire. The two modern receptors are thought to descend from an ancestral corticosteroid receptor, which underwent a gene duplication. Hereafter, I'll refer to the receptors as the corticosteroid receptor and the aldosterone receptor, hoping that all the jargon won't obscure the message.

In a widely-discussed paper published in Science a year ago (Bridgham et al., Science 2006), Thornton's group determined the most likely DNA sequence of this ancestral gene, then "resurrected" it, meaning simply that they created that very DNA sequence in the lab. (Determining the ancestral sequence was a nifty piece of work; actually making the DNA is quite straightforward, especially if you have a little dough.)

Their experiments showed that the ancestral receptor could bind to a hormone that didn't exist yet (aldosterone) while it was functioning as a receptor for corticosteroids. In other words, the receptor was available for activation by aldosterone long before aldosterone was around. (All jawed vertebrates make corticosteroids, but only tetrapods make and use aldosterone, an innovation that occurred at least 50 million years later.) The modern corticosteroid receptor has since lost its ability to interact with aldosterone, and Bridgham et al. chart the most likely evolutionary path, at the molecular level, by which we and other tetrapods came to have a corticosteroid receptor that won't bind to aldosterone. The surprising result, however, is the fact that the ancient receptor was able to bind aldosterone, millions of years before aldosterone is thought to have been present.

The 2006 paper is, I think, more notable as an illustration of an important evolutionary principle ("molecular exploitation" is the authors' term) than as a set of observations; Michael Behe's trashing of the group's work is disgusting, but it's true that the findings are limited in scope. It's worth having a look at the whole paper, though (and I believe it's freely available with free registration), because the authors very clearly explain the rationale for their continuing work, which is to begin to address one of the major "gaps in evolutionary knowledge": the mechanisms underlying stepwise evolution of "complex systems that depend on specific interactions among the parts."

If you're well-read on ID thought, that last sentence should sound pretty familiar. So let's note that prominent papers in science's premier journals are acknowledging that the evolutionary mechanisms that generate complex structures -- including "irreducibly complex" systems -- are as yet poorly understood. And let's give ID credit for asking a good question. (Not a new one...but a good one.)

The 2006 paper did not, as advertised, utterly destroy ID arguments, and again Behe is right to criticize the near-hysteria surrounding that work. But I find Behe's bravado otherwise unconvincing. Because that paper did set up the most recent work, and the whole story illustrates rather clearly how ID's question will (soon) be answered.

The most recent paper adds significantly to the picture, and introduces some genetic concepts that Behe's fans should pray he understands. The authors (Ortlund et al.) took their analysis to a far more detailed level, by extending their previous observations to include much more of the receptor family tree. In the 2006 work, they had assembled a detailed family tree for the receptors, by looking at DNA sequences from living species known to represent various branches on the tree of life. In other words, they chose organisms such as lampreys, bony fish, amphibians and mammals, and examined their DNA codes (for the receptors) to find the changes that occurred in each branch of the lineage. Now, please stop and think about this, because it's really cool. What the authors did was mine existing databases of DNA sequence data, pulling out the sequences of the steroid receptors from 29 different vertebrate species. You could repeat this part of the experiment right now, by referring to their list of organisms in Supplemental Table S5, which provides the ID codes needed to locate the DNA sequences in the Entrez Gene database. Then they charted the changes in the DNA sequence in the context of the tree of life as sketched out in the fossil record. The tree they assembled includes all the steroid receptors, and I've annotated it a little if you want to have a look. They used this tree to guide their further experiments, as I'll explain below. What the most recent paper added to the story was an analysis of the 3-D structure of the various postulated intermediates in the evolutionary pathway. The authors accomplished this by making proteins from the "resurrected" genes, then crystallizing them and using X-ray diffraction techniques to determine their precise structures.

Examination of their receptor family tree revealed something interesting. Most vertebrates have highly specific receptors: the corticosteroid receptor isn't strongly stimulated by aldosterone, and vice versa. But some living vertebrates (skates, in particular) show a different pattern: the corticosteroid receptor isn't all that specific for cortisol. Because the ancestral receptor also lacked specificity (as shown in the 2006 paper), the authors concluded that the receptor acquired its discriminating taste at some point between the branching-off of skates (and their kin) and the separation of fish from tetrapods. Their Figure 1 is a little crowded, but it illustrates this nicely:

To follow the evolutionary narrative in this graph, start at the blue circle, which represents the ancestral receptor that was "resurrected" in the 2006 paper and that happily binds to both corticosteroids and aldosterone. (The graphs on the right side of the figure demonstrate the specificity, or lack thereof, of the receptors at different times in history.) There's a branch leading up and to the left, to the various GRs (corticosteroid receptors), and one leading up and to the right, to the MRs (aldosterone receptors). At the green circle, another branching event occurred, 440 million years ago, at which point certain groups of fishes (skates among them) branched off, up and to the right. The receptor at that point is an ancestral corticosteroid receptor, and it still isn't specific for corticosteroids. But the receptor at the yellow circle, in the common ancestor of tetrapods and bony fishes, is specific. The authors conclude that specificity arose between those two points, between 420 and 440 million years ago. With some (deliberate?) irony, they indicate that process with a black box.

The rest of the paper explores the pathway by which the receptor might have been successively altered so as to install specificity for cortisol. During those 20 million years of evolution, at least 36 different changes were introduced in the makeup of the receptors. By looking at the 3-D structures of the ancestral forms, the authors were able to discern the specific functional ramifications of these various changes, and they found that the alterations fell into three groups:
  • Group 'X' alterations included the changes reported in the 2006 article. These are the biggies, that account for much of the functional 'switch' between GRs and MRs. These alterations don't account for the specificity change that occurred inside the black box in Figure 1.
  • Group 'Y' alterations are all strongly conserved (meaning that they were permanent changes), and occurred during the black box time period. Moreover, this group of changes is always seen together: modern receptors have all of these alterations, while ancestral receptors have none of them.
  • Group 'Z' alterations are also conserved changes, but they don't always occur together like group 'Y'.
The authors set about the work of examining the function of "resurrected" receptors bearing these groups of changes. When they introduced group 'X' changes into the ancestral receptor, they got a receptor that was almost modern (i.e., specifically tuned to cortisol) but not quite; this was what the previous work had indicated. Then they hypothesized that the group 'Y' changes, because they were so highly conserved and because they all occurred together, would make the transition complete. But no: instead, the group 'Y' alterations made the receptor worthless, unable to bind any hormone at all. Surprise! Looking at their 3-D structures, they figured out what this meant. The group 'Y' changes were somehow important, but they could only have a beneficial influence in the presence of another set of alterations, group 'Z', which had to occur in advance. The biophysical details don't concern us, but the basic idea is that the group 'Z' changes created a permissive environment for the group 'Y' changes, which are the alterations that complete the development of the modern specific form of the receptor for cortisol.

In genetics, we have a word for this type of interaction between genetic influences: epistasis. The fascinating history of steroid receptor evolution includes examples of what the authors call "conformational epistasis," meaning that some alterations in 3-D structure are required in advance for other alterations to ever get off the ground. Specifically, some alterations are evolutionary dead ends, because they yield worthless proteins, unless those alterations follow another set of changes that generated a different -- and more fruitful -- environment.

The authors then construct a map of what they call "restricted evolutionary paths through sequence space," showing how you can get there from here, without traversing an evolutionary no-man's-land of non-function. The path includes changes that don't apparently improve the receptor, but that yielded the right environment for the changes that did improve function. Their map is in Figure 3:

The idea is that you want to get from the lower left corner of the cube (the ancestral receptor) to the upper right corner (the modern receptor) without hitting a stop sign (a worthless receptor). The green arrows indicate a change in function of some kind, the white arrows no change. Yes, you can get there from here.

The authors note that their data "shed light on long-standing issues in evolutionary genetics," firstly the question of whether adaptation proceeds through "large-effect" changes (mutations), or through baby steps. Their conclusion:
Our findings are consistent with a model of adaptation in which large-effect mutations move a protein from one sequence optimum to the region of a different function, which smaller-effect substitutions then fine-tune; permissive substitutions of small intermediate effect, however, precede this process.
They note that the large-effect changes are inherently easier to identify (of course), and that the painstaking work of "resurrecting" the ancestral proteins and studying their function is the only way to identify the critical small-effect alterations that made the "big jump" work.

The authors also comment on the big "contingency" debate. I'll write more on the whole "rewinding the tape of life" question some other time; for now, we'll just consider the authors' words:
A second contentious issue is whether epistasis makes evolutionary histories contingent on chance events. We found several examples of strong epistasis, where substitutions that have very weak effects in isolation are required for the protein to tolerate subsequent mutations that yield a new function. Such permissive mutations create “ridges” connecting functional sequence combinations and narrow the range of selectively accessible pathways, making evolution more predictable.
If you have read my summary of the wormholes in morphospace story, this metaphor of "ridges" should make a little sense. The authors here are describing the same concept: an evolutionary exploration of a design space, with paths meandering through a map of the possibilities. But:
Whether a ridge is followed, however, may not be a deterministic outcome. If there are few potentially permissive substitutions and these are nearly neutral, then whether they will occur is largely a matter of chance. If the historical “tape of life” could be played again, the required permissive changes might not happen, and a ridge leading to a new function could become an evolutionary road not taken.
The history of the steroid hormone receptor, then, appears to include several different aspects of evolutionary biology combined: "chance" creating opportunity, leading (via epistasis) to selection for improvement, all done step by step, with some steps generating more apparently dramatic change than others.

Amazingly, Michael Behe is pretending that this analysis is utterly unimportant, with no implications at all for ID proposals, because the receptor-hormone system isn't "irreducibly complex." Some critics of ID claim that the goalposts are being regularly moved, and I'm inclined to agree. But let's just grant Behe the difference between protein-hormone interactions and protein-protein interactions. Does anyone really believe that Joseph Thornton's work doesn't show us exactly how the "irreducible complexity" challenge is going to fare in the near future?

11 October 2007

More required reading

As a Christian biologist (and now Christian biologist blogger), one of my goals is to help Christians understand biology. And right now, that means I need to focus on helping Christians see the worthlessness of most of the ideas in the Intelligent Design movement, and especially to help Christians see how embracing ID is both theologically and intellectually unwise.

Well, John Farrell is a an ally, and he's a great read. Check out his blog, at Farrellmedia, which he describes as "reports and commentary on the news, science, and creative ends of the media." Among other things, Farrell seems to be particularly interested in (and annoyed by) the enthusiasm of conservative publications like The American Spectator and National Review for the ideas of ID. (I don't follow those publications closely at all anymore, but I have noticed with alarm the fondness for ID that is displayed at Books and Culture.) I've added one of his books, The Day Without Yesterday, to my must-read list. (Just what I need. I haven't even finished The Sonnets.) Last month, a post on John's blog spawned a long discussion at Touchstone. Enlightening, in various ways.

I've also added The Fire and the Rose to my blog list. It's the blog of one D.W. Congdon, a seminary student at Princeton. There you'll find some interesting discussion of theology, science, and, most notably for me, concepts of the soul and the Imago Dei. One of my favorite posts: "Can we still speak of the soul?" My best friend is mentioned in that article.

Finally, I recommend Gordon Glover's blog, based on his book Beyond the Firmament. I haven't read the book (Steve Martin reviews and recommends it over at Evangelical Dialogue on Evolution), but Gordon's comments here and his work on the blog make it clear that he and I have a very similar approach to science and faith.

Now before I get back to work on my slowly-gestating article on evolution of new proteins, I thought I should explain why my articles don't come out every three hours: I'm actually a working scientist -- currently on sabbatical in the lab of a friend and collaborator -- and, well, doing experiments is just as fun as writing about them.

Take that, PZ.

08 October 2007

"The gift is not like the trespass"

Our family embraced the Reformed tradition (of evangelical Christianity) while we were a part of Park Street Church in Boston. We have many fond memories of our time at Park Street; I first picked up a copy of Del Ratzsch's excellent Science and Its Limits from the church library there, and it was at Park Street where we first learned about Calvin College. But right now, I'm remembering the many times when I heard a particularly excellent sermon, the kind of sermon that makes you feel as if you're hearing simple and well-known truths for the first time. If you're a Christian, perhaps you know what I'm talking about. This past Sunday, I had one of those experiences. The text was Romans 5:12-21, and when my friend Rev. David Kromminga was finished, I had that weird feeling like I'd never read Romans 5 in my life. It's worth sharing here, because the text is one that surfaces amid creationist objections to evolutionary theory.

If there is any problem at all between evolution and Christian belief, it arises in the context of the historical narrative of redemptive history. (The notion that evolutionary theory, as a natural explanation, is hostile to Christian belief is, in my opinion, preposterous. Hence my low regard for ID.) Specifically, the historical nature of the Fall, in which sin and death entered the world due to the actions of two particular people, is difficult to fit into the narrative of common ancestry.

In my view, the problem is simply historical (the stories don't seem to fit well together), but many Christians see a more serious conflict, because they believe that the existence of a single historical Adam is central in the redemption narrative. In fact, I'm sure that the vast majority of evangelicals would take this position. And Romans 5 would be a big reason why.

The standard proof text is this one: "Therefore, just as sin entered the world through one man, and death through sin, and in this way death came to all people, because all sinned..." (Romans 5:12, TNIV). The basic claim, that sin entered through Adam, is repeated three more times in the passage. Moroever, the passage clearly sets up Adam and Christ as types to be compared. No list of "dangers of theistic evolution" would be complete without reference to Romans 5.

I think this is sad, because it seems to me that Paul is trying to say something much bigger than "Adam brought death, Christ brings life." The problem with that summary is that it strongly intimates a kind of equality between the two types, as though Adam's sin was "cancelled out" by Christ's redemptive work. What Paul is saying, I think, is something like this: "don't think for a moment that one of those is equal to the other." Verse 12: "The gift is not like the trespass." Or, as David put it on Sunday: "the rot does not equal the redemption." Read the whole passage; Paul's repetition suggests that he is determined to make sure we get that message.

I agree that the "historical Adam" question is a tough one. But I'm not sure it's enormously important. Adam was the "dirt man." Jesus is the God man. The gift is not like the trespass. Let's not compare the God man to the dirt man, as though they're two sides of the same coin. And let's not forget that Jesus is the author and finisher, the beginning and the end. Even if we never figure out how that whole dirt-man thing actually went, we'll know everything we need to know if we know the God man.

04 October 2007

Sympathy for the Devil's Chaplain (Part II)

Long before Richard Dawkins topped the charts with his recent entry into the folk-religion genre, he was reviled by Christian culture warriors as a Public Enemy, an ayatollah of atheism, the embodiment of the evil that ensnares all who embrace Darwin's Dangerous IdeaTM. His revivalistic fervor, combined with his, um, expertise in handling the media, makes him a near-perfect spokesperson for unbelief, and consequently he is credited with some now-famous pronouncements on subjects related to faith and science.

Now to be sure, some of Dawkins' more colorful and/or controversial statements are indefensible, and his fellow atheists at least occasionally point this out. (I do think that unbelievers should be more willing to disavow some of his truly sickening behavior, but if atheists asked me for quid pro quo, I'd need to blog 10 hours a day just on the subject of evangelical Christian misconduct.)

But this is the second of two articles in which I do penance for referring to the Devil's Chaplain as an 'idiot.' So I'm not going to catalog his misdeeds/misstatements. Instead, I'll to pick a few of his more famous sentences and explain why every Christian's favorite materialist mullah is often just being brutally frank.

First, let's acknowledge that sometimes Dawkins is misunderstood and/or misrepresented. The first few chapters of The Extended Phenotype, as I explained in my previous post, involve Dawkins' careful exposition of the ways in which his ideas had been misconstrued, sometimes wildly so. For a more recent example, consider the whole "brights" episode. In the summer of 2003, Dawkins and fellow atheist apostle Daniel Dennett launched a campaign (in the UK and USA) to get atheists more respect. They called on fellow unbelievers to adopt the label "bright," analogous to the label "gay" successfully adopted by homosexuals. Many Christians I know found this to be arrogant and offensive, mostly because they connected the dots and interpreted "bright" to be the opposite of "dumb" or "dim." Dennett has specifically disclaimed this intention (see also page 21 of Breaking the Spell), and I'm taking his word for it. So, let's not waste our time demonizing Dawkins for offhand comments that may not reflect what he really believes.

Here, then, are some of Dawkins' better-known remarks, and my comments.

1. "Undisguised clarity" or arrogance?

It is absolutely safe to say that if you meet somebody who claims not to believe in evolution, that person is ignorant, stupid or insane (or wicked, but I'd rather not consider that).
--from a review of Blueprints: Solving the Mystery of Evolution, in the New York Times, 9 April 1989
Ah yes, this is, I think, The Mother of All Richard Dawkins Quotes. It's provided fodder for Christian critics of all stripes, essentially all of whom express indignation and outrage. I see two types of responses. One response is universal: everyone who attacks the statement says that it is arrogant or bullying. The other is specific to anti-evolution critics: they say (of course) that it is wrong. In this latter camp, we find young-earth creationists denouncing Dawkins with typical vitriol, but also "skeptics" like Alvin Plantinga, who insist that there can be reasoned doubt about evolutionary explanations.

On the first count, while I agree (as do other atheists) that Dawkins can be abrasive and insensitive, I am generally uninterested in controversies surrounding etiquette. There are, of course, appropriate and inappropriate ways to tell someone that they don't have a bloody clue what they're talking about, but I know just how hard it can be to remain patient while being regaled (for the umpteenth time) with all the stock objections to evolution. (My most recent little piece of hate mail came from a man who shamelessly confessed to having first learned all the biology he needed to know from a local weatherman. I AM NOT MAKING THIS UP.) Yes, there is probably a nice way to say "you're wrong about that," but (perhaps owing to my Scottish ancestry) I'd rather be clearly corrected than have to sit through all the fawning disclaimers.

I think Dawkins was trying to say "evolution is beyond a reasonable doubt" in a dramatic and attention-getting way. And he succeeded. Now, was he displaying arrogance or intolerance? I'm quite sensitive to this charge; it has been thrown at me by at least one evolution-bashing colleague. I do worry about being arrogant, at least because I'm not (usually) trying to be obnoxious. But, as Dawkins noted in a subsequent reflection on criticism of the quote in question: "undisguised clarity is easily mistaken for arrogance." Was he being over-the-top obnoxious? Intolerant? Insensitive? Well, let's have a look at a little of the context of the quote:
We are not talking about Darwin's particular theory of natural selection. It is still (just) possible for a biologist to doubt its importance, and a few claim to. No, we are here talking about the fact of evolution itself, a fact that is proved utterly beyond reasonable doubt. To claim equal time for creation science in biology classes is about as sensible as to claim equal time for the flat-earth theory in astronomy classes. Or, as someone has pointed out, you might as well claim equal time in sex education classes for the stork theory. It is absolutely safe to say that if you meet somebody who claims not to believe in evolution, that person is ignorant, stupid or insane (or wicked, but I'd rather not consider that).

If that gives you offense, I'm sorry. You are probably not stupid, insane or wicked; and ignorance is no crime in a country with strong local traditions of interference in the freedom of biology educators to teach the central theorem of their subject. I recently toured East Coast radio stations, doing phone-ins. I came away optimistic. I had expected hostile barracking from creationists with closed minds. Instead, what I found was genuine curiosity and honest interest. I got sincere questions from intelligent people who really wanted to know because they had literally no education in evolution.
--from a review of Blueprints: Solving the Mystery of Evolution, in the New York Times, 9 April 1989
When the quip is put back into its native habitat, I find it to be provocative but not inappropriate. It can be paraphrased, in my opinion, as follows: "If you claim to doubt evolution, then I'm quite sure this is because you don't know much about it. I can think of a few other reasons, but they're not nearly as likely, and some of them wouldn't reflect well on you." And I do think that the context makes clear that Dawkins is specifically addressing common descent.

Which brings us to the second response to the quote: that it is wrong, because there is plenty of room for reasonable doubt regarding common descent. In my view, common descent is indeed beyond a reasonable doubt. (If I felt like dealing with the different meanings of the word 'evolution,' I would have typed them here.) And so, like Dawkins, I think there are relatively few means by which one would arrive at rejection of common descent. Ignorance is by far the most commonly-traveled path. Stupidity sure isn't going to help. Insanity is not worth discussing. Wickedness...well, some people do seem to, um, prevaricate about evolutionary science, but come on: that's not what Dawkins was saying. He was saying this: if you doubt common descent, you either don't understand it, or you are refusing to understand it. And to Dawkins, this refusal to understand, this willful ignorance if you will, is insane, stupid, even wicked.

Now, it's important to note that Dawkins was referring to common ancestry in his comments. Many Christian critics imply that Dawkins was denouncing any and all skepticism of evolutionary theory. I think the fuller context of his remarks makes clear that this criticism is invalid.

But is ignorance really the only reason why a reasonably intelligent person might reject common ancestry? In his follow-up, Dawkins allows that his analysis may have been incomplete:
There is perhaps a fifth category, which may belong under 'insane' but which can be more sympathetically characterised by a word like tormented, bullied or brainwashed. Sincere people who are not ignorant, not stupid and not wicked, can be cruelly torn, almost in two, between the massive evidence of science on the one hand, and their understanding (or misunderstanding) of what their holy book tells them on the other. I think this is one of the truly bad things religion can do to a human mind. There is wickedness here, but it is the wickedness of the institution and what it does to a believing victim, not wickedness on the part of the victim himself.
It is here that I part with Dawkins, at least a little. I know people who doubt common descent (more specifically, universal common descent), not because they are ignorant of the data or of the explanation, but because they have an additional data set that needs to be taken into account. These folks understand the Bible to be making certain factual claims about the age of the earth or of the nature of the Fall. They know, full well, why scientists accept common descent as a scientific explanation, but are searching for a rival explanation that also enfolds the "biblical data." As I've written before, I think these people are mistaken about the "biblical data," but they are not torn, tormented, bullied, brainwashed. You can probably tell that I respect the ideas and work of these young-earth creationist theorists vastly more than those of the Intelligent Design movement. Similarly, I find Alvin Plantinga's (now dated) criticisms of evolutionary science to be embarrassingly weak (even in their time), but when he expresses doubts based on possible points of factual conflict with Christian belief (i.e., the assertion that humans were created "specially"), then his skepticism cannot be dismissed using Dawkins' rubric.

2. Darwin made me an atheist.
Darwin made it possible to be an intellectually fulfilled atheist.
-- from The Blind Watchmaker (1996 Edition), page 6
Plenty of Christians are convinced that evolution is a particularly sharp implement in the Devil's toolbox; some creationists seem convinced that the theory is at the root of every known evil. (Adam must be relieved.) Certainly many are quite sure that accepting evolution is a big step toward unbelief.

And that's what Richard Dawkins thinks, right? Well, maybe, but here's that quote in its complete context:
...what Hume did was criticize the logic of using apparent design in nature as positive evidence for the existence of a God. He did not offer any alternative explanation for apparent design, but left the question open. An atheist before Darwin could have said, following Hume: 'I have no explanation for complex biological design. All I know is that God isn't a good explanation, so we must wait and hope that somebody comes up with a better one.' I can't help feeling that such a position, though logically sound, would have left one feeling pretty unsatisfied, and that although atheism might have been logically tenable before Darwin, Darwin made it possible to be an intellectually fulfilled atheist.
-- from The Blind Watchmaker (1996 Edition), page 6 (italics in original)
In other words, Darwin provided a natural explanation for a previously-unexplained set of observations -- granted, a vast and overwhelmingly impressive set of observations -- namely, "endless forms most beautiful" in living creations. But really, that's all Darwin did, and I think that's all Dawkins is saying here. This matters to atheists, I presume, because unexplained stuff (of any kind) makes them uncomfortable. Providing a natural explanation for anything -- comets, hurricanes, pleasure, pain, neuronal development -- makes the world a little more comfy for an atheist. And that makes sense to me. As Alvin Plantinga puts it: "...evolution serves to answer what would otherwise be a crushing objection to naturalism."

I think Dawkins is surely right about all this, but I think it's a mistake for Christians to overemphasize his otherwise indisputable assertion. First of all, while scientific explanations might make it easier for an atheist to sleep, they ought not affect the slumber of a believer, unless that believer, like Dawkins, has anchored her/his belief in natural phenomena that can't be explained. I reject the notion of God as an Explanation, and I'm distressed by the impression that so many of my fellow Christians feel so compelled to find unexplained phenomena, so as to label them "God's work." Second of all, I think it's a dangerous thing to suggest that people become atheists because of a scientific theory. Maybe that's because, as a Reformed Christian, I don't think it's nearly that easy to separate someone from the love of Christ. And finally, I am uncomfortable with the notion, upon which whole ministries seem to be based, that scientific explanations (or lack thereof) are strongly linked to belief. Doesn't Hebrews 11:3 say something different?

3. Believing without evidence?

Richard Dawkins, the scientist's scientist, actually confessed that he has religious belief -- in evolution. He said that he would believe it even if it were unsupported by evidence. No, really:
Even if there were no actual evidence in favour of the Darwinian theory (there is, of course) we should still be justified in preferring it over all rival theories.

Even if the evidence did not favour it [evolution], it would still be the best theory available!
-- from The Blind Watchmaker (1996 Edition), pages 287 & 317 (italics in original)
Oh, the fun that ID people have had with these. Outside the intended context, it does look like Dawkins is advocating "blind faith" in evolutionary theory, as though he embraces the theory only to escape the clutches of a loathed rival. Whether or not Dawkins sees evolution that way, the quotes above are not what they seem, and in fact they are assertions with which I handily agree.

Let's take the second quote and put it back into the paragraph from which it was excerpted:
The theory of evolution by cumulative natural selection is the only theory we know of that is in principle capable of explaining the existence of organized complexity. Even if the evidence did not favour it, it would still be the best theory available! In fact the evidence does favour it. But that is another story.
-- from The Blind Watchmaker (1996 Edition), page 317 (italics in original)
Here Dawkins is doing something that I tried to do in my first post on this blog: he is separating the evidence for evolution from the explanatory power of evolutionary theory. Notice that he didn't write, "Even if the evidence contradicted it..." In fact, Dawkins loves to relate the response of J.B.S. Haldane to the question of whether and how evolution could be falsified: "fossil rabbits in the Precambrian." It's really not reasonable at all to suggest that Dawkins is claiming that one ought to accept evolution in spite of the evidence, and the rest of the chapter ("Doomed rivals") from which the quotes are taken makes this quite clear.

What Dawkins is saying, I think, can be paraphrased like so: "We ought to prefer evolutionary theory over its rivals, whether or not there is more evidence in favor of evolution, because the theory is the only one that provides a compelling natural explanation for biological complexity." You don't need to be an atheist, or a "Darwinian fundamentalist," or wicked or insane, to agree. You need only be a person who prefers natural explanations for the natural world, a person who thinks that the formation of the wonders of God's biological creation can be understood by some of those very wonders.

Okay, I'm done with my penance. Back to the Journal Clubs; I have a backlog of articles worthy of our attention.

03 October 2007

It's October in Boston...and in Phoenix

I did promise to make baseball a part of this blog, and so far it's been all sorts of serious stuff about science and faith. And now it's October! We all know what that means. In fact, it's going to an excellent fall in the Matheson household, for we are fans of two major league teams: first and foremost, the Boston Red Sox, and second, the Arizona Diamondbacks. (I'm from Phoenix and my wife Susan is from Tucson; 3 of our 4 children were born in Tucson; the fourth in metro Boston.) Those two teams own the best regular-season records in their respective leagues. Woo hoo! The Sox won tonight, and the D-backs are playing some hapless Midwestern team as I write this.

Well, if you are not yet excited about postseason baseball, but would like to be, I offer the following exercise. It involves neither of our favorite teams, but is based instead on one of the most outstanding plays in postseason baseball history. Now if you will, please work through the steps in order.

1. Make sure your computer's sound is on, loud.
2. Listen to this broadcast excerpt. Just listen to the whole thing. If you don't know exactly what is happening, you can come back after you've completed the exercise.
3. Watch the video of the event. You'll see a link called "350K" next to a description of the achievement.
4. Watch this video at YouTube. Listen for the desperate plea while the ball is in flight. (The same person is screaming a few seconds later.)

If that doesn't help you get ready for the MLB postseason, then you're probably a soccer fan, and that means we should get back to science and faith, in hopes that we have some common ground...

Go Sox!

(For those readers who are unhappy, perhaps because they loathe the Mets or any team from Gotham, try this out. It's from 2004.)