evo-devo

Science has a very important paper in the current issue about the evolution of a gene enhancer in hominids, expressed in forelimb development and concentrated toward the first digit. The enhancer is a conserved sequence named HACNS1, it exhibits a stronger signature of recurrent selection on the human lineage than any other conserved enhancer sequence. In transgenic mice, the human version of this enhancer triggers gene expression in the forelimb, concentrated toward the thumb side, and some other parts of the body, notably the pharyngeal arches (which give rise to elements of mouth, throat and larynx), eye and ear. The research is by Shyam Prabhakar and others at Lawrence Berkeley National Lab, and involves Edward Rubin and James Noonan, otherwise prominent in the Neandertal genome sequencing.

I think this is an extraordinarily important result. You don't see me write those words very often. This is a paper that every biological anthropologist should read. It gives an extremely good example of the importance of developmental regulation to human evolution. We will see many more papers like this one in the coming years. This is one of the genes that makes us human.

Ed Yong of Not Exactly Rocket Science has written a nice online review of the research, and Science has accompanied it with a perspective piece by Gregory Wray and Courtney Babbitt. Here's a quote from that article:

To test the function of this region, they genetically engineered mouse embryos to express a construct composed of human HACNS1, the promoter element of a heat shock gene, and a reporter gene. Their results show that human HACNS1 drives expression in the mesenchyme of the early developing forelimb, and later developing hindlimb, in these mouse embryos. A comparison of expression patterns driven by macaque, chimpanzee, and human orthologs of HACNS1 revealed that consistently strong forelimb expression is a unique property of the human version. By testing various combinations of human and chimpanzee HACNS1 sequences, the authors narrowed down the relevant functional mutations to an 81-base pair region containing 13 substitutions that arose during human evolution. This concentration of substitutions is highly unusual relative to the genome as a whole, implying positive selection on this region during human origins.

The press are going with the story that the evolution of this gene may underlie the unique evolution of human manual dexterity. It's a good hypothesis, but I think there is a more accurate way of putting the situation. We see that the enhancer has effects in different areas of the developing embryo. Its action is therefore pleiotropic: changing its function in one area might well screw up its action somewhere else. So at the very least, this is an enhancer that must satisfy multiple constraints. Strong evolutionary change in its sequence may reflect changes in one of those functions, or more than one. But at the very least, it implies that the hominid developmental program not only satisfies different fitness constraints than in the human-chimpanzee common ancestor, but that these changes required repeated changes.

We don't know how long it would have taken all these nucleotide substitutions to happen. But we might find signs in the fossil record of such a sequence of events, if we had enough bones, and if we had more information about the effects of different forms of the gene on the adult phenotype. For example, the relatively long thumbs of the Hadar hominids (compared to chimpanzees and gorillas) suggest that the sequence of changes started early in hominid evolution. There's a hypothesis.

But like I said, I wouldn't rule out other possible functions of the enhancer as targets for selection. It is plausible (as a hypothesis) that the enhancer with the most selected substitutions on the human lineage might be more likely than others to have been selected for multiple functions. And we have plenty of reasons to suspect selection on its other targets, particularly the developing mouth, throat and ear.

It may even be that the evolution of human thumbs was a side effect of evolution in the throat, or vice versa. That's the kind of weird world evo-devo makes for us!

References:

Prabhakar S and 9 others. 2008. Human-specific gain of function in a developmental enhancer. Science 321:1346 - 1350. doi:10.1126/science.1159974

Wray GA, Babbitt CC. 2008. Enhancing gene regulation. Science 321:1300-1301. doi:10.1126/science.1163568

Stories about genetics, paleoanthropology, and other stuff have been falling this week faster than I can keep up, but happily I'm not alone. Here are some of the more interesting blog-takes on recent stuff:

Pigment use by Neandertals

Julien Riel-Salvatore writes about recent work by Maria Soressi and Francesco d'Errico establishing that Mousterian pigment nodules were used as crayons:

The reason why this ongoing study is so convincing is that the authors used replicative referents that objectively establish the microscopic and rugosimetric features of blocks of coloring materials worked in different manners and with different tools. This provides an objective baseline against which to compare the characteristics of objects found in assemblages attributed to Neanderthals and to determine whether they bear evidence of having been purposefully manufactured by human action.

I'll write more about this when I get a chance, but Julien's post is valuable and provides translated (from French) excerpts of the relevant papers.

Genetic diversity in African cattle

Razib writes about a New York Times Magazine article that details the cultural and economic pressures around cattle breeding in Uganda. People are bringing in Holsteins, because even though they are finicky in the African climate, they can give as much as 20 times the milk of the native Ankole cattle. The Ankole breed resembles those that American cattlemen would call "Watusi."

Here's a passage from the article:

Not everyone in Uganda, however, agrees that the foreign breeds are an upgrade. President Yoweri Museveni once imposed a ban on imported semen. Museveni belongs to the Bahima ethnic group. When he was a baby, in a sort of Bahima baptism ritual, his parents placed him on the back of an Ankole cow with a mock bow and arrow, as if to commit him symbolically to the defense of the family's herd. Museveni, now in his 60s, still owns the descendants of that very cow, and he retains a strong bond to the Ankole breed. Two years ago, I accompanied a group of Ugandan journalists on a daylong trip to one of the president's private ranches, where he proudly showed us his 4,000-strong herd of Ankole cattle. At one point, a reporter asked if the ranch had any Holsteins. "No, those are pollution," Museveni replied. "These," he said, referring to his Ankoles, "the genetic material is superior."

Razib's comment on another passage:

I guess it's nice that [the author] put quotes around [genetic] dilution, but the rest of the article suggests to me that the author hasn't internalized that genetics is discrete, and that information isn't destroyed through cross-breeding. Rather, it seems that a good program of cross-breeding could result in a superior breeds of Holstein optimally suited to the local climate. That's what happened with indigenous African lineages as they hybridized with introduced South Asian ones 2,000 years ago to produce the Ankole according to the article! This sort of piece in a widely circulated publication such as The New York Times Magazine could have been a serious examination of agricultural and quantitative genetics, and just how much we depend on these unsexy sciences to feed the world. As it is, there's a lot of hand-waving scare-mongering....

The usual argument in favor of preserving diversity of domesticated species is as a hedge against future uncertainties like climate change or novel diseases. Another reason is to preserve local flavor -- that's why people grow "heirloom" vegetables, for instance. But it is quite certain that the pasturage devoted to traditional breeds of cattle well decline if imported breeds provide a net economic advantage. In that case, the best way to preserve diversity is cross-breeding -- which also has the direct advantage of introducing locally adapted genes into the descendants of the foreign breed.

This is what African herders have been doing for thousands of years, as evidenced by the spread of zebu genes across the continent. These European imports are merely the newest version.

What are genetic tests good for?

Hsien-Hsien Lei has an invited post by Ann Turner, noted for her book, Trace Your Roots With DNA. Turner comments on the new genetic tests from deCODEme and 23andMe:

Since I'm interested in genetic genealogy, I am more attuned to the ancestry components of the deCODEme results. The admixture results are interesting to anyone who suspects they may have ancestors from different geographical areas. The detailed chromosome graphs also show the potential for tracing segments of DNA shared with even more distant relatives. For instace, it was recently found that a block carrying a colon cancer gene could be traced back to a couple who arrived in the US in the early 1600's. This sort of thing might very well show up in the "Compare Me" feature.

Evo-devo and its detractors

On the subject of guest posts, Carl Zimmer is running an essay from Jerry Coyne. The essay is a response to a blog post by Olivia Judson, in which she reviewed the ideas of Richard Goldschmidt and suggested that the macromutation theory may be primed for a comeback, using recent results from evolutionary developmental biology (evo-devo) as a jumping-off point. Coyne has been one of the foremost critics of the idea that evo-devo is somehow "changing" basic conceptions in evolutionary biology.

Unfortunately, her piece is inaccurate and irresponsible, especially for a journalist with a strong science background (Judson has a doctorate from Oxford). I've admired Judson's columns and her whimsical and informative book Dr. Tatiana's Sex Advice to All Creation. But this latest posting is simply silly. As an evolutionary biologist, I'm used to seeing our field twisted out of shape to satisfy the demands of journalists who love sensational new findings--especially if they go against long-held Darwinian beliefs like the primacy of gradual, stepwise evolution. But I'm not used to seeing one of my own colleagues whip up excitement about evolutionary biology by distorting its findings.

I have to say I find the entire concept of a "New York Times blog" to be interesting. They have quite a lot of them now, and they are not clearly demarcated from other editorial content at the Times website. That's not a criticism, but it does mean that readers tend to think they come with the full authority of the Times' editors. To me, they read just like any other blog post anywhere, but for a picture of how people perceive their importance, just look at their comment sections.

That was enough in this case to bring Jerry Coyne out of the woodwork. I think his slapdown is a little extreme (Remind me not to get on his bad side!). But Judson was clearly mistaken to equate today's evo-devo results with Goldschmidt's ideas -- a link that evolutionary developmental biologists themselves deny. At any rate, Coyne's forceful advocacy for his point of view makes for good reading, and I would recommend it to anybody interested in where evolutionary developmental biology is going and how it will influence our ideas about evolution over the next few years. Here at Wisconsin I am at one of evo-devo's epicenters, and I can see a number of ways that it may transform our ideas of human evolution. So in that sense, I am more sanguine than Coyne about the prospects for understanding morphological changes with developmental insights. At the same time, I agree substantially that the genetic questions must ultimately be answered in genetic terms.

The discussion in Zimmer's comments section digresses into what Stephen Jay Gould may or may not have thought about saltational changes in evolution. I think that is essentially unenlightening, in the sense that quote-pulling out of Gould can reinforce almost any point of view.

Seed is running a little article on the evolution of language, by lingust Juan Uriagereka:

A quasi-paradox has persisted within the field of linguistics, because the sudden emergence of such a complex, limitless system in a single species is hard to rationalize in terms of standard evolution. Its rapid spread makes language seem more like a viral epidemic that swept through the human population rather than a trait inherited through the typical dynamics of evolution.

Luckily, two recent advances have made it possible to rigorously address the problem of language's evolution for the first time. Molecular biology (including the publication of the human genome) and the so-called evo-devo paradigm now permit us to establish new and often quite unexpected connections among very different species. In addition, linguists' understanding of syntax -- how words are strung together into grammatical sentences—has developed to the point where language can be broken down into its basic procedural components. These components can now be seen to resemble traits observed in other species -- with functions that appear to be completely unrelated to familiar thought processes. Language may indeed be unique to humans, but the processes that underlie it are not.

It hits on many of the big topics, including the comparative biology of communication in finches, the regulatory role of FoxP2 in birdsong, and the brain processes underlying syntax.

I will differ from Uriagereka on this point:

The publication of the Neanderthal genome should tell us just how different their FoxP2 gene really is from our own.

Human FoxP2 differs from chimpanzees by two derived amino acid substitutions. If Neandertals were different from us (which seems likely, given the recent evidence of selection on the gene), then they would have had only one of these substitutions. It's an answer we don't actually need the Neandertal genome for. Now, if only we could start thinking about some other language-related genes.

This week's NY Times Science section is devoted to evolution, with articles by:

Carl Zimmer, on microbial evolution

John Noble Wilford, on human paleontology

Nicholas Wade, on recent human genetic evolution

Carol Kaesuk Yoon, on evo-devo

An essay by Douglas Erwin, about evo-devo and Darwinism

A video interview with my UW colleague, Sean Carroll

And several other things. I will be reading through these articles over the next several days and providing some annotation and commentary -- I think they are an interesting compilation of recent (and some older) developments in evolutionary science.

I think many biologists have a pretty vague picture of why Linnaeus was important. To some, he probably seems banal -- how exciting could it be to make all those lists of species, just endless lists, over and over? "Yeah, sure, somebody had to come up with a classification system, but mainly, I'm sure glad it didn't have to be me!"

Other biologists may view Linnaeus through a lens clouded to some extent by the later development of evolutionary theory. Linnaeus is certainly the most familiar, and possibly the most apt, example of essentialist, typological thought prior to Darwin. His categorizations depended on typological features, and even today definitions of species based on morphological types are often called "Linnean species."

But several aspects of Linnaeus' writings belie this stereotype. For one thing, especially later in his career, Linnaeus became convinced that new species actually do appear over time, particularly through hybridization. I'll have more on that in a later post.

Another thing is that before Linnaeus and his contemporaries, people didn't approach biological diversity with an essentialist framework. An essentialist view of species required the assumption that species were fixed, not changing over time. A good source discussing the importance of Linnaeus in the formulation of species fixism is Ronald Amundson's book, The Changing Role of the Embryo in Evolutionary Thought.

I posted on Amundson's take on Weismann a couple of years ago. I think his take on Linnaeus and species fixism — although short — was the part of the book that struck me the most, mainly because of its heterodoxy in contrast to the historical work of Ernst Mayr and others.

To begin, he lays out the conventional story:

Modern narratives of the history of evolutionary biology take place against the background of species fixism. The story goes like this: The historical discovery of evolution was the overthrow of species fixism. From ancient days, Western intellectuals had conceived of a stable and unchanging world that had been created by God in pretty much the condition it now exists. Beginning in the early seventeenth century, traditional beliefs were shaken by a series of challenges to the world's constancy and stability ... [e.g., Copernican cosmology, geological process]. In this narrative, the fixity of species was the last vestige of the stable and unchanging world of the ancients.... Darwin's job was like that of Copernicus — the overthrow of an ancient belief in stability.

That's the story, but it's not true. The Western tradition was indeed centered on an unchanging world but the fixity of species was not a part of that world. It became widely accepted for the first time both among naturalists an theologians during the eighteenth century, only about a century before Darwin (Zirkle 1951:48-49; Zirkle 1959:642). Carl Linnaeus is widely known for his unequivocal statements of species fiexism and special creationism. It is less widely recognized that Linnaeus was one of the innovators of fixism. Prior to Linnaeus and his botanical colleagues, beliefs in transmutation and spontaneous generation were extremely widespread (Amundson 2005:34-35, emphasis in original).

For his story, it is important for Amundsen to spends some time describing belief in transmutation, and he devotes three pages to various illustrations of how widespread the belief was. I especially like the following passage on the "barnacle goose," which serves to set the background against which species fixism seems a starkly modern view:

Even more dramatic transmutations were commonly accepted. To the modern ear they strain the boundary between myth and honest empirical belief. The story of the phoenix was often treated skeptically, but it was no less extreme than the barnacle goose. The Oxford English Dictionary still contains the renaissance term anatiferous: "producing ducks or geese, that is producing barnacles, formerly supposed to grow on trees and dropping off into the water below, to turn into tree-geese" (Hacking 1983:70). Philosopher Ian Hacking uses the term anatiferous to illustrate incommensurability: Wht in the world could those people have been thinking of? But this was an honest factual belief. Raven quotes the sixteenth-century author Scaliger, who reports "as a thing he himself has seen" the stories "falsely told of the phoenix but veraciously of the Bernacle [sic] Goose" (Raven 1953:204).

Most people, sometime during the slow years of high school biology, learn about Francesco Redi and Lazzaro Spallanzani — Redi put rotting meat in a jar with gauze over the top, proving that maggots don't spontaneously generate; Spallanzani showed that microbes don't spontaneously generate but come from the air and may be killed by boiling. Both, and others such as van Leeuwenhoek, helped to roll back the idea that life was generated from nothing. Still, the problem with refuting spontaneous generation is that you have to be able to see all possible influences. Not until Pasteur was the idea of microbial spontaneous generation finally refuted once and for all.

Now, to bring the connection to Linnaeus -- Spallanzani's work on boiling and microbial transmission was in the 1760's. Spallanzani also demonstrated that sperm was necessary for reproduction (at least in mammals), performing the first known artificial inseminations (of dogs) -- all this in 1779, just after Linnaeus' death.

In other words, in Linnaeus' day, spontaneous generation and transmutation were still potent ideas. For animals in particular — not Linnaeus' strong point — they were quite difficult to disprove. Even the causes of reproduction were somewhat mysterious, and what radical transmutations were possible at birth were well-known.

Botanists, including Linnaeus and his contemporaries, were in a much better position to establish the limits to variation. In this respect, Linnaeus' close focus on the sexual processes of plants and consequent classification were hugely important. Botanists' long experience in plant breeding experiments, and with the relative ease of exchanging seeds and cuttings across Europe, they developed an ability to assess the properties of hybrid strains and varieties -- even more than a hundred years before Mendel.

Spontaneous generation and transmutation are ultimately linked, since both predict very particular things about reproduction and the nature of parent-offspring resemblances: like from like, and nothing from nothing are joined principles.

Seen in the context of prefixist theories of spontaneous origins and transmutations, species fixism was a progressive scientific development. Beliefs in spontaneous generation persisted into the nineteenth century, but they were restricted to smaller and smaller organisms as time passed (Roe 1981). Fixism was established for nonmicroscopic plants and animals around 1750, primarily on the basis of plant breeding experiments. Plant variation had been an especially common area of transmutationist beliefs. The careful and controlled breeding programs of Linnaeus and others established fixism among most naturalists (Amundsen 2005:37).

Amundsen argues for Linnaeus' dual importance -- not only as the innovator of his system of taxonomic descriptions and classification, but also as an experimenter and gatherer of information about botanical forms:

Linnaeus's fixism, like that of his contemporaries, was based on evidence that had been painstakingly gathered from a vast network of horticultural gardens across Europe. The old transmutationist beliefs in the influences of climate on plant forms had been tested by returning the modified forms to their original locations. The plants then reverted to their original forms. Experiments had been done in the production of hybrids ("bastards"), and the limitations on viability and fertility had made it seem exceedingly unlikely that this was a cause of new species (Amundsen 2005:40).

This "painstaking" work underlay the basic scientific description of variability under human domestication between Linnaeus and Darwin. Plants might be changed in new environments, and they might be bred or hybridized by humans, but they would revert to their wild, "natural" state. Stamos (2005:91) discusses Linnaeus' view of this reversion:

Linnaeus, for example, exhibited a belief in the law of reversion in his Critica Botanica (1737) when he wrote that "every day new and different florists' species arise from the true species so-called by botanists, and when they have arisen they finally revert to the original forms. Accordingly to the former have been assigned by Nature fixed limits, beyond which they cannot go: while the latter display without end the infinite sport of Nature" (Ramsbottom 1938: 200n).

And Stamos (ibid.) quotes further from Jussieu, in many ways Linnaeus' taxonomic successor:

Jussieu too, in his Genera Plantarum (1789), expresses a belief in the law of reversion. Although a species, he says, "is occasionally subverted for a while by chance or human industry; that is to say, some individuals may vary one from another on account of location or climate or disease or cultivation . . . But these varieties, obeying the law of nature, . . . return to the primordial species, their character restored, if other factors do not interfere" (Stevens 1994: 340-341).

Hence, reversion served as evidence that species are fixed, and that their variation is transient. Botanical experimentation supported the essentialist view of species, against the tranmutationist view.

The belief in fixism was important to the classification -- if organisms could readily transmute to radically different forms, then a "natural" classification of them would likely be impossible. Linnaeus' classification was not itself a "natural system", but his hierarchical use of characteristics -- and recognition that reproductive features were the basis of large-scale similarities in plants -- put the outline of such a system in view.

References:

Amundson R. 2005. The changing role of the embryo in evolutionary thought: roots of evo-devo. Cambridge University Press, Cambridge UK.

Stamos DN. 2005. Pre-Darwinian taxonomy and essentialism -- a reply to Mary Winsor. Biol Phil 20:79-96. doi:10.1007/s10539-005-0401-9

The PNAS early edition includes a paper by Michael Tress and (many) others about the frequency of alternative splicing across the genome. I wrote about alternative splicing in January, and this post about new developments in the study of RNA rewards reading if you missed it the first time.

The new paper examines a small subset of known functional loci for which the splicing pathways have been well-studied. Here's the abstract:

Alternative premessenger RNA splicing enables genes to generate more than one gene product. Splicing events that occur within protein coding regions have the potential to alter the biological function of the expressed protein and even to create new protein functions. Alternative splicing has been suggested as one explanation for the discrepancy between the number of human genes and functional complexity. Here, we carry out a detailed study of the alternatively spliced gene products annotated in the ENCODE pilot project. We find that alternative splicing in human genes is more frequent than has commonly been suggested, and we demonstrate that many of the potential alternative gene products will have markedly different structure and function from their constitutively spliced counterparts. For the vast majority of these alternative isoforms, little evidence exists to suggest they have a role as functional proteins, and it seems unlikely that the spectrum of conventional enzymatic or structural functions can be substantially extended through alternative splicing.

The short description of the ENCODE project is worthwhile:

The pilot project of the Encyclopedia of DNA Elements (ENCODE) (11), which aims to identify all the functional elements in the human genome, has undertaken a comprehensive analysis of 44 selected regions that make up 1% of the human genome. One valuable element of the project has been the detailing of a reference set of manually annotated splice variants by the GENCODE consortium (12). The annotation by the GENCODE consortium is an extension of the manually curated annotation by the Havana team at The Sanger Institute (Tress et al 2007:5495).

The main conclusion of the paper is that, even though alternative splicing is very common, in most cases the splicing "isoforms" are nonfunctional. Splicing provides a mechanism for the evolution of many distinct proteins from a small number of genes, but the variation in splicing only rarely leads to two or more functional proteins as an outcome. This raises the question of why cells tolerate multiple splices for a gene. We pretty much have to conclude that the nonfunctional splices do not have a fitness cost.

Still, splicing may provide a mechanism for creative evolutionary changes in some cases:

The standard path of protein evolution is usually conceived of as
stepwise single base-pair mutations. In contrast alternative splicing typically involves large insertions, deletions, or substitutions of segments that may or may not correspond to functional domains, subcellular sorting signals, or transmembrane regions. The deletion and substitution of multiple exons seen in many of these transcripts suggests that splicing is not always a mechanism for delicate and subtle changes and, as a process, may be rather more revolution than evolution (Tress et al. 2007:5499).

They describe a few cases where alternative splices lead to disease, or are associated with abnormal cellular metabolism during -- particularly in cancer. In this sense, we have the usual range of functional implications from any kind of genetic change: rarely, something good results; often the change makes no difference, but sometimes it's really bad. The observation that a fairly large set of nonfunctional spliced proteins may be floating around cells means that this class of variants joins many of the transcribed RNA elements as part of the cytoplasmic menagerie.

References:

Michael L. Tress and 46 others. 2007. The implications of alternative splicing in the ENCODE protein complement. Proc Nat Acad Sci USA 104:5495-5500. doi:10.1073/pnas.0700800104

The introduction of game theory into evolutionary biology is often credited to George Price and John Maynard Smith. This is for good reason; together they were able to generalize Hamilton's (1967) work on parental investment strategies. By doing so, they provided an account of the evolution of variant strategies of many kinds from a gene-centered perspective.

Before their landmark contribution, there had been earlier forays attempting to integrate a game theoretic perspective into evolutionary terms. Hamilton's own work was immensely important, since his "unbeatable strategy" concept was a clear precursor of the ESS concept. Additionally, we should include the series of papers by Richard Levins (e.g., 1963), which considered the optimum adaptive solutions for various problems relating to spatial and temporal changes in the environment. These didn't explicitly involve the terminology of game theory, but dealt with the mathematical conditions under which variant strategies would pay off.

But the earliest major paper was Richard Lewontin's "Evolution and the Theory of Games," published in 1961 (and presaging Maynard Smith's own 1982 book of the same title). This paper introduced the concepts of game theory to many biologists, and some of them started playing with the ideas in interesting ways that weren't ultimately integrated into the later development of evolutionary game theory.

Waddington on game theory

One of these interesting early efforts is a short paper by C. H. Waddington (1965), which served as an introduction to a symposium on the evolution of colonizing species. Waddington discussed Lewontin's 1961 paper in some detail, and used it to frame the problem of colonizing versus noncolonizing species. He took these two alternatives as possible strategies that a species might adopt in its contest against Nature.

This is an unusual formulation from the perspective of later evolutionary game theory, and reminiscent of "good of the species" Wynne-Edwards-type thinking, but Waddington lays it out very clearly:

In the "evolution game" which it is playing, a species has to contend with unforeseen eventualities which the future may bring -- a new parasite, a new predator, possibly an Ice Age. Another element of uncertainty arises from the fact that there may be several different ways in which the species makes a place for itself within the whole ecological network available for its exploitation -- it could change its food habits or length of life cycle, or it could migrate to another locality, and so on. The game it is playing is perhaps best formulated as a zero-sum three-person game, the players being (1) the species or population under consideration, (2) the whole environment, organic as well as inorganic, that impinges on that species, and (3) the bio-system that would occupy the living sace of first player, if it were eliminated. This third player may include species which are also involved in the second player, but by formulating the game in this way, the third player is reduced to a dummy whose only function is to absorb the gains and losses of the first player; in this way we retain the advantages of dealing with a zero-sum game and only have to consider the moves of two players, the species and Nature (Waddington 1965:2).

In the next sentence, Waddington defines the "score" of the game as the number of offspring produced by the first player in the succeeding generation, which of course is easily scaled to the population mean fitness. In my mind, this shows the "game theoretic" description here to be a conceit, since he is not really describing a situation different from the ordinary assumptions of population genetics. Indeed, his description of the "third player" is entirely superfluous from this point of view.

But I find the conceit illuminating, because it reminds us that there are other species there to absorb Nature's gains. A species must compete in reproductivity at a high level due to these interspecific interactions, or it will not last. Later in the book, Lewontin describes some models where the typical viability fitness of the mean genotype is far less than unity, which of course means that the fertility of these genotypes must be very high, indeed, for them to manage to survive. These are only modeling questions, but the possibility of losses against the field are important to the models.

He goes on to describe the game as an interdemic process, in which different populations within a species may adopt different strategies:

A population has, of course, no intelligence of its own which would make it possible for it to choose which move to make, i.e., to adopt a strategy. But no large population is fully panmictic; it is always broken up, if only by distance, into a number of smaller subpopulations which are partially independent in genotype. Each subpopulation will make a somewhat different move, some of which will be more successful and others less; a global or "Monte Carlo" strategy will emerge as that sequence of moves that has proved most successful up till the stage the game has reached. As we shall see, there are really many different games going on simultaneously, affecting different levels of individual and population organization, and each game elicits a corresponding strategy (Waddington 1965:2-3).

The point of his paper is to suggest that colonizing may be a strategy that is adaptive under some circumstances and not in others. The theme is developed later in the volume by Edward O. Wilson, Ernst Mayr, and Lewontin, and I may post a bit on those contributions later.

What I found provoking in Waddington's paper was this passage:

At a fundamental biochemical level, there are alternative strategies possible in the organization of the genetic control of enzyme seqeunces. Consider a metabolic pathway in which successive steps are catalyzed by enzymes P, Q, R, S, T, .... As Kaeser (1963) has pointed out, in some cases it is found that one of these enzymes, say R, is rate-determining for the whole sequence of steps, the throughput being highly dependent on the quantity or activity of R, but little affected even by considerable changes in the activities of the other enzymes; in other metabolic pathways, all of the enzymes may have more or less equal importance in controlling the over-all flow through the system. If the first strategy is adopted, the system is little affected by mutations or environmental effects controlling the nonrate-determining enzymes, but is very sensitive to effects on R; with the second strategy, the system is affected somewhat by mutations or other influences on any of the enzyme proteins, but is not affected drastically by any of them. The second would therefore seem to be the Minimax strategy, but a species might often be able to get away with the first gambit, in which it would only rarely suffer any loss of efficiency, at the expense of failing completely in a few individuals (Waddington 1965:4).

With this "first strategy", Waddington is describing a strategy for developmental robusticity: resistance to alteration in the developmental program due to alterations in the genetic background. For example, some developmental programs continue to generate adaptive outcomes even if there is a knockout mutation in one of their essential genes. We could say that these systems "degrade gracefully," so that many kinds of mutations lead to phenotypes that are not markedly reduced in fitness. Yet a few of the key genes in most systems cannot tolerate such changes. These developmental programs have evolved in such a way that reduces the impact of most mutational variants in their essential genes, but has emphasized the impact of others.

Now, this kind of structure might be a necessary consequence of genetic and developmental networks. Maybe it just isn't possible to build a genetic system like Waddington's hypothetical every-gene-equally-crucial example.

But the current trend in evo-devo is to propose that such network structures (so called hub-and-spoke networks) are themselves selected based on optimizing some biological property, such as modularity or reliability. Optimality theory and game theory are closely conceptually related to each other -- Maynard Smith was a central figure in the introduction of both to evolutionary biology -- but few studies of developmental processes seem to have explicitly focused on the idea of alternate developmental strategies.

Switches, canalization, and genetic variation

Waddington is best known for his concept of developmental canalization (I posted a quick review of the topic early last year). In this paper, he suggests canalization as one of a set of four developmental strategies that might be adaptive in different environmental contexts:

In order to meet the demands of differeing environmental effects on development, and on selective pressures, a species has, in general, to preserve considerable genetic variation within its populations. But this variation can be deployed in a number of ways: (a) The species can become very good at producing one particular phenotype under almost any circumstances, relying upon the environment always offering a possibility for this phenotype to get by. This leads to the evolution of systems of developmental canalization of the phenotype...

In other words, genetic evolution tends to reduce the effect of environmental variance on the phenotype. That insensitivity to environmental (and background genetic) variability is canalization.

...(b) The species can become good at doing one or another of a few alternative things. This leads to switch mechanisms between canalized phenotypes, e.g., in species which have hot and cold weather or aquatic and terrestrial forms. (c) The species can allow the environment to have a strong influence on individual ontogeny, provided it is ensured that the environmental modifications are toward the selection optimum for that particular environment. This leads to the evolution of developmental systems which are highly adaptable. (d) The species can have a development which is relatively unaffected by normal environmental variations, but in which most genetic changes come to phenotypic expression, and can rely on its wealth of genetic variation always to throw up some phenotypes near the selection optimum. This leads to systems in which there are considerable random or periodic changes in the gene pool from time to time, but little genearl long-term movement in any particular direction (e.g., fluctuations in inversion frequencies according to season, as in some species of Drosophila (Waddington 1965:4-5).

This list is worth remembering: (a) canalization, (b) developmental switches, (c) environmental variance, (d) genetic variance.

I did a little noodling around and found that a few people have followed up on this idea that developmental robusticity versus plasticity may be treated in a game theoretic perspective. For many purposes, the benefits and drawbacks of a given developmental program may be examined without reference to the idea of strategies. Still, plasticity itself is presumed to be adaptive to changing environments, so that the system of benefits and drawbacks in particular environmental contexts (and their frequency) may be usefully considered in ESS terms. Some have picked up on this analogy and mentioned the relation between a plastic developmental program and a "mixed strategy" ESS solution.

Lively (1986) considered the case of "developmental switches" in a game theoretic context. Picking up on the work of Levins (1963) and Levene (1953), Lively examined the circumstances under which organisms may adapt a stress-tolerant phenotype. Such phenotypes may be adaptive to low-resource environments, or cold, or high-predator environments. The possibility of such stress-tolerant phenotypes presents some complexities for interpreting

If the inducing cue [in the environment] is highly correlated with the harsh patch and rare in the benign patch, a conditional strategy can be stable over a wide range of patch frequencies, and this range increases with increasing cost to the stress-tolerant morphology. Hence, a change from one patch type to the other over geological time could result in a correspondingly "rapid" change in morphology without speciation or even any genetic evolution. This would happen without a trace of intermediate forms. Care must be taken, therefore in interpretation of the fossil record when developmental conversion is suspected to be an alternative to strict genetic determination of morphology (e.g., Reyment 1982) (Lively 1986:569).

The relevance of such stress-tolerant phenotypes might seem to be clearer for short-lived, high-predation animals than for hominids.

But there are obvious applications of the idea of developmental strategies in human evolution. For one thing, the maturation time is a prime target of research into fossil humans. A long series of papers has been devoted to uncovering whether Neandertals developed on the schedule of modern humans or some other (presumably more ape-like) schedule. Only recently has this literature brought in the substantial variation in dental development time among recent human populations.

As yet, the subject of nutrition-induced variation in development time has not been a major topic in papers examining skeletal development in Neandertals or other early humans. The normal phenotypic response to developmental stresses in humans is to elongate the developmental span, delaying maturation and/or truncating body size. The relevance of stress-tolerant phenotypes is reasonably clear in this context.

Lively also elaborates on the game-theoretic properties of such a system, including a surprising observation about variant strategy morphs:

The present study also shows that interactions among morphs are required for a mixture of unconditional strateies (i.e., genetically determined polymorphism) to ba an evolutionaily stable state of the population. Hence, we have the apparent paradox that, in the absence of mutualistic effects, genetically determined morphs must compete in order to coexist. This result is analogous to results gained from genotypic models, which show that density dependence is required for the maintenance of allelic polymorphisms (Maynard Smith 1962, 1970; Anderson and Arnold 1983). The competitive interactions within and between morphs may be completely symmetrical (all e_ij = e), provided there is some cost associated with the stress-tolerant morphology [if the stress-tolerant morphology had no costs, it would be the only ESS]. Asymmetrical competition that favors the nontolerant morph in the benign patch further increases the range of patch frequencies over which genetically determined morphs may coexist, but this region is narrow even under hte best of conditions. This narrowness may explain why so few genetically determined polymorphisms are observed amon randomly dispersing organisms (Lively 1986:569, emphasis mine).

I also found some work that places development into the perspective of another of my current interests, information theory. Thomas Getty (1996) suggested that developmental plasticity may be interpreted as a signal reception problem. An organism will maximize its fitness if it can adopt the pattern of development that is most adaptive to the environment in which it lives. If we consider a population in which individuals may find themselves in two environments with different requirements, then a plastic developmental program might allow individuals to develop in the way appropriate to one of these environments. This is the classic problem also treated by Levins with relation to environmental heterogeneity. Under certain patterns of different environments, a population may optimize its fitness by retaining or evolving plasticity.

Getty points out that a plastic developmental program with conditional expression of different phenotypes requires some way to detect which environment the organism is in:

The genotype, in effect, discriminates among possible environments on the basis of cues. Although it has long been reconized that the evolution of phenotypic plasticity hinges on the availability of reliable cues (Levins 1963; Lively 1986), most recent analyses do not explicitly consider the role of cue discrimination (e.g., Houston and McNamara 1992; Kawecki and Stearns 1993; de Jong 1995; Via et al. 1995). In contrast, Moran (1992) focuses on the role of cues and concludes that they are a dominant factor limiting conditional developmental switching. At the heart of her analysis is a probabilistic relationship between (proximate) environmental cues and (ultimate) environmental quality within generations. This probabilistic relationship suggests that "reliable cues" are like "noisy signals" in signal detection theory (SDT). In both cases, there are risks that a response will not correctly match the ultimate conditions. I want to show that it is useful to think of this aspect of phenotypic plasticity as a signal detection process (Getty 1996:378).

The term, "bet-hedging" comes up frequently in these kinds of considerations. Sometimes organisms simply don't have access to high-quality (i.e., minimal noise) signals of their environments, at least not at the important stages of early development when significant phenotypic choices must be made. But the higher the fitness payoff from betting correctly on a phenotype-environment match, the higher the risk an organism should be willing to take on the basis of its necessarily limited information.

Predicting the future

Of course, the value of better information-processing mechanisms is clear: if an organism can predict its environment with more certainty, then it can adapt with greater plasticity because the risk of a poor match between phenotype and environment will be greatly reduced.

This relation comes up again and again from the consideration of phenotypic plasticity and environments. Generally, phenotypic variation is adaptive to more predictable environments.

Sound counter-intuitive? Surely, it seems that the way to adapt to a more variable environment is with a variable phenotype?

Indeed, not so. Phenotypic variation is just as likely to make an organism less adapted to a varying environment as more adapted. This is worse than a wash if the environment is unpredictable. The best that selection can do in an unpredictable environment is to minimize heritable (i.e., the genetic component of) phenotypic variation. This is purely a loss-cutting measure, since in generations where the environment is very different from the maximally adapted value, the population fitness will tank. Still, a variable population would be worse, because much of a phenotypically variable population will do poorly even under the mean environment!

Levins (1963) shows that a more predictably changing environment allows another response. In such an environment, the presence of phenotypic variation can allow selection to track environmental changes. So predictability is the key to adaptability by selection.

Levins considered the case where the environment was predictable because it was temporally autocorrelated -- in other words, one generation's environment predicts the next. We may instead consider predictability that emerges from signals available in the environment. An organism that can detect such signals has a way to maximize its adaptation -- choosing the phenotype that is most adaptive to the current environment.

In terms of Waddington's four developmental possibilities; Levins is testing two of them: the canalized phenotype versus the phenotype with substantial genetic variance.

As Getty describes, the signals that would permit an organism to choose between these strategies are typically noisy: they entail substantial errors of reception. You might bet on a cold year because the groundhog sees its shadow, but how often is the groundhog right, really?

It is an open question whether human intelligence once enhanced fitness by better reading the signs that predicted future environments. I think this is unlikely because there is a scaling problem -- take an organism with a lifespan as long as a human, and try to predict the course of the environment in a given area over that timespan. It's certainly beyond me.

But one argument is that human culture really constitutes Waddington's option (c): human behaviors are extensively induced by the environment, allowing a "highly adaptable" response to changing environments.

Information about the environment may smooth the fitness function, so that a given amount of environmental fluctuation presents a smaller fitness cost. This could occur either because information reduces mortality (allowing individuals to survive immediate shortfalls), or because it permits higher fertility. Both are intimately related to energy (how much food is available), nutritional ecology (how much protein is available), and group structure (how many mates are available).

This implies a certain kind of ecology for ancient humans, one with some surprising correlates. More on that later.

References:

Getty T. 1996. The maintenance of phenotypic plasticity as a signal detection problem. Am Naturalist 148:378-385.

Hamilton WD. 1967. Extraordinary sex ratios. Science 156:477-488.

Levene H. 1953. Genetic equilibrium when more than one ecological niche is available. Am Naturalist 87:331-333.

Levins R. 1963. Theory of fitness in a heterogenous environment. II. Developmental flexibility and niche selection. Am Naturalist 97:75-90.

Lewontin RC. 1961. Evolution and the theory of games. J Theor Biol 1:382-403.

Lewontin RC. 1965. Selection for colonizing ability. Pp. 77-94 in The Genetics of Colonizing Species, Baker HG, Stebbins GL, eds. Academic Press, London.

Lively CM. 1986. Canalization versus developmental conversion in a spatially variable environment. Am Naturalist 128:561-572.

Maynard Smith J, Price GR. 1973. The logic of animal conflict. Nature 246:15-18.

Waddington CH. 1965. Introduction to the symposium. Pp. 1-7 in The Genetics of Colonizing Species, Baker HG, Stebbins GL, eds. Academic Press, London.

My earlier post introduced the conserved noncoding elements shared by vertebrates. Those elements shared by vertebrates seem to be crucial to regulating developmental genes, and are not found in any invertebrates. Now a current paper by Tanya Vavouri and colleagues reports that other conserved noncoding elements have evolved in parallel in worms.

I'm posting it because it gives another good mini-introduction to these conserved seqeunces in vertebrates:

Comparisons of the human genome against the genomes of distantly related vertebrates have revealed an abundance of highly conserved non-coding elements (CNEs) that appear to have been 'frozen' throughout vertebrate evolution [1-7]. The exact number of elements shared between any set of species varies depending on the precise definition of similarity and the divergence of the genomes used. For example, a comparison of the human genome against the mouse and the rat genomes revealed that all three share 256 elements with no evidence of transcription that are 100% identical over at least 200 base-pairs (bp) [2]. Furthermore, the human genome and the genome of the Japanese pufferfish (Fugu rubripes), which diverged from a common ancestor approximately 450 million years ago (MYA), share 1,373 CNEs, with an average length of 199 bp and average identity of 84% [4].

A striking property of human CNEs is that they cluster in genomic regions that contain genes coding for transcription factors and signaling genes involved in the regulation of development ('trans-dev' genes) [2-4,6]. Therefore, CNEs have been proposed to act as cis-regulatory sequences for these trans-dev genes. In support of this, where tested, the majority of assayed CNEs can act as tissue-specific enhancers for a transgene in zebrafish or mice [4,7-10].

So it looks like the first ten references in the paper are an essential group to review in terms of outlining the regulation of vertebrate developmental genes. I've pasted them in below; it's a field that has originated largely within the last three years.

References:

Vavouri T, Walter K, Gilks WR, Lehner B, Elgar G. 2007. Parallel evolution of conserved non-coding elements that target a common set of developmental regulatory genes from worms to humans. Genome Biology 8:R15. doi:10.1186/gb-2007-8-2-r15

1. Boffelli D, Nobrega MA, Rubin EM: Comparative genomics at the vertebrate extremes. Nat Rev Genet 2004, 5:456-465.

2. Bejerano G, Pheasant M, Makunin I, Stephen S, Kent WJ, Mattick JS, Haussler D: Ultraconserved elements in the human genome. Science 2004, 304:1321-1325.

3. Sandelin A, Bailey P, Bruce S, Engstrom PG, Klos JM, Wasserman WW, Ericson J, Lenhard B: Arrays of ultraconserved non-coding regions span the loci of key developmental genes in vertebrate genomes. BMC Genomics 2004, 5:99.

4. Woolfe A, Goodson M, Goode DK, Snell P, McEwen GK, Vavouri T, Smith SF, North P, Callaway H, Kelly K, et al.: Highly conserved non-coding sequences are associated with vertebrate development. PLoS Biol 2005, 3:e7.

5. Dermitzakis ET, Reymond A, Antonarakis SE: Conserved non-genic sequences - an unexpected feature of mammalian genomes. Nat Rev Genet 2005, 6:151-157.

6. Vavouri T, McEwen GK, Woolfe A, Gilks WR, Elgar G: Defining a genomic radius for long-range enhancer action: duplicated conserved non-coding elements hold the key. Trends Genet 2006, 22:5-10.

7. McEwen GK, Woolfe A, Goode D, Vavouri T, Callaway H, Elgar G: Ancient duplicated conserved noncoding elements in vertebrates: a genomic and functional analysis. Genome Res 2006, 16:451-465.

8. Nobrega MA, Ovcharenko I, Afzal V, Rubin EM: Scanning human gene deserts for long-range enhancers.
Science 2003, 302:413.

9. de la Calle-Mustienes E, Feijoo CG, Manzanares M, Tena JJ, Rodriguez-Seguel E, Letizia A, Allende ML, Gomez-Skarmeta JL: A functional survey of the enhancer activity of conserved non-coding sequences from vertebrate Iroquois cluster gene deserts. Genome Res 2005, 15:1061-1072.

10. Goode DK, Snell P, Smith SF, Cooke JE, Elgar G: Highly conserved regulatory elements around the SHH gene may contribute to the maintenance of conserved synteny across human chromosome 7q36.3. Genomics 2005, 86:172-181.

A subset of evolutionary theorists are specifically concerned with how the evolution of multiple characters of organisms are linked to each other by genetic correlations. A handful of those theorists actually think about human evolution. There is a little bit of matrix algebra involved; maybe that explains why the number is so small -- I don't know.

But the problem is of fundamental importance to quantitative evolution, because the power of selection to change a feature is constrained by the genetic relationships of that feature to other features of the organism.

For example -- want to make the brain bigger? Then you have to deal with the fact that some of the same genes that make brains bigger also make bodies bigger. Want to make the neocortex bigger in particular? It will be hard to do it without increasing the size of the brain, the size of the body, the size of the teeth, and so on. All these sizes are genetically correlated to some extent, the actual extent being described by the genetic variance-covariance matrix (often called G). Each of these characters has its own pattern of (often stabilizing) selection, so if you push on one very much, others will pull against you.

Massimo Pigliucci (2006) knows a lot of quantitative genetics. He even has a textbook about it. He also has a paper in Biology and Philosophy, titled "Genetic variance-covariance matrices: a critique of the evolutionary quantitative genetics research program." So this attracted my interest -- what is a well-known quantitative geneticist doing critiquing the research project of quantitative genetics?

It has a pretty provocative abstract:

This paper outlines a critique of the use of the genetic variance-covariance matrix (G), one of the central concepts in the modern study of natural selection and evolution. Specifically, I argue that for both conceptual and empirical reasons, studies of G cannot be used to elucidate so-called constraints on natural selection, nor can they be employed to detect or to measure past selection in natural populations - contrary to what assumed by most practicing biologists. I suggest that the search for a general solution to the difficult problem of identifying causal structures given observed correlation's has led evolutionary quantitative geneticists to substitute statistical modeling for the more difficult, but much more valuable, job of teasing apart the many possible causes underlying the action of natural selection. Hence, the entire evolutionary quantitative genetics research program may be in need of a fundamental reconsideration of its goals and how they correspond to the array of mathematical and experimental techniques normally employed by its practitioners (Pigliucci 2006:1).

That's some big talking -- "fundamental reconsideration of its goals". Do his specific critiques of the application of the genetic variance-covariance matrix support this conclusion?

His first point is that the theoretical work on "the" G matrix leaves very open the structure of particular G matrices that one might study in one or another organism. Some covariances among characters are stable at high taxonomic levels, like the family level, and other covariances may be very different from one population of a species to another. He writes:

The upshot of this is that quantitative geneticists who focus on stamens in Brassicaceae are likely to reach completely different conclusions about the stability of the genetic variance-covariance matrix from their colleagues who instead study leaf evolution in semi-aquatic plants. Indeed, research by Waldmann and Andersson (2000) in populations of Scabiosa columbaria and S. canescens found, among other patterns, that 'the magnitude of (co)variances was more variable among characters than among populations,' i.e., the results of a given study of G depend more strongly on which traits the investigators choose to focus on then it does on the species selected! Again, this ought to be obvious, but much of the literature is written in a way that implies that the evolution of G is a single kind of thing, and that it makes sense to think of G itself, somewhat independently of the particular traits used to calculate it (Pigliucci 2006:8).

I think that does pose a theoretical problem (i.e., what is the relationship of theory to empirical results-on-the-ground), but it doesn't pose any particular problem for people studying specific traits in a specific group of organisms -- for instance, cranial form in the hominids. At that level, we don't care about G matrices in general, or even the total genetic variance-covariance matrix for the human body, as long as we can estimate the variances and covariances of the characters we are studying. So the global problem may not affect the specific implementations.

Pigliucci's second point carries more force, and to my mind is really a concatenation of two separate issues. First, we have some practical means that we may use to estimate genetic variances and covariances -- such as half-sib breeding designs. But we have no justification for the further assumption that the variances and covariances obtained from such experiments actually apply to any natural populations. The second, and related, issue is that the "true" G matrix in a natural population depends on its breeding structure.

If anything, these points have more force applied to the specific example of human evolution than to the general case. For one thing, for most characteristics we don't even have any studies of the genetic variance and covariance with other characters. A lot of studies just substitute the phenotypic variance-covariance matrix, assuming that it is "more or less" like the genetic matrix.

And there is an awful lot of simply using phenotypic variances and covariances without mentioning genetics at all! As in, "population X and Y cluster phenotypically near each other, therefore they are genetically close to each other."

The second part is something to consider more closely. Have hominids changed their breeding structure in ways that would make difference to the genetic correlations among traits? Hard to say. Seems like changes in group size and within-group relatedness would make a difference, but I'm not sure about the scale.

Pigliucci's third point concerns the use of G, which is always a local estimate, to examine long-term patterns of evolution:

As with h², if the available genes or the gene frequencies in the population change, so too might G; similarly, in a different range of environments (or if the population becomes differently distributed among the environments encountered), G might well change. Given this, if one wants to make use of G in simulations of long-term evolution (e.g., Via 1987), one must assume that the matrix stays constant (or at least proportional) to the ancestral state over the time period one is investigating (generally thousands of generations). But several authors (e.g., Turelli 1988; Pigliucci and Schlichting 1997) have pointed out that this is highly unlikely on first principles, because evolution de facto changes gene frequencies, and therefore G itself; nor is it unreasonable to suppose that over such time periods the environment encountered by the population may change as well. Therefore, while it is sensible to assume near-constancy of G for short-term applications (e.g., crop or animal breeding, artificial selection experiments, or perhaps even evolution in wild populations over few generations), the hypothesis of approximate constancy becomes less and less likely the more widely separated the relevant populations are in time and/or space (Pigliucci 2006:10-11).

He notes that the same argument applies to variation in environments, as does to time.

I would personally say that this is the most serious problem. If the genetic variance-covariance matrix evolves, as it must for phenotypic evolution to occur, then it cannot be assumed constant. I have many times heard the argument that we can estimate variances and covariances for fossil humans by using large samples of living humans -- because living humans are more or less similar in their variances and covariances to ancient humans. (These are, of course, phenotypic variances and covariances, since the idea of genetics rarely enters!) But this idea is simple nonsense, particularly since it is usually made in an effort to show just how different some fossil sample is from living people!

Pigliucci's fourth point is best described in his own words:

More philosophically interesting are problems concerning G that cut to the core of why biologists use the concept to begin with. Let us start with the notion that the predictability of future phenotypic evolution is predicated on G revealing 'constraints' on evolutionary change imposed by the 'genetic architecture' underlying complex phenotypes. The idea is that trade-offs between traits to which an organism can allocate available resources (for example, between survival and reproduction) should manifest themselves as observable (negative) genetic covariances between the traits in question. If this were true, studies of G matrices could reveal features of the underlying trade-offs that influence the direction of phenotypic evolution, a major goal of evolutionary biology. Unfortunately, work by Houle (1991) and Gromko (1995) has dealt what should have been devastating blows to these uses of G in evolutionary theory; oddly, despite these key papers being published in Evolution, the premier journal in the field, their arguments have scarcely made a dent in the literature (Pigliucci 2006:12).

He goes on to describe the results. Houle demonstrated mathematically that trade-offs do not always give rise to negative genetic covariances, because the genetic covariances depend on the genetic variances and the number of genes involved. Large variances at many genes may outweigh even strong negative covariances at few genes. Gromko demonstrated many different pleiotropic mechanisms might generate the same G matrix, and that the pattern of covariances cannot distinguish between different possible evolutionary outcomes. In particular, covariances near zero might occur for systems that nevertheless are highly constrained in their coevolution.

More than other problems, this one would seem to reveal a conflict between evolutionary developmental (evo-devo) approaches and standard quantitative genetic approaches. Where standard approaches might view the genetic variance-covariance matrix as the genetic structure, evo-devo looks for the mechanisms that give rise to the stucture. Since different functional relationships among genes might give rise to the same covariances, this gives some reason for caution in applying the covariances to predict long-term evolution.

Pigliucci's fifth point is that G matrices don't provide much help in distinguishing the effects of selection from those of genetic drift. This is an important theoretical problem in biology and one that has been applied to evolutionary transitions in human evolution (e.g., the cranial form of early Homo). Pigliucci gives a review of the predictions of standard theory (viz., selection should affect different sets of characters differently, drift should affect the entire matrix in a proportional way), and then describes Drosophila experimental work that raises problems for the theory:

When these authors [Phillips et al., 2001] considered the average G across populations (a statistically useful, but biologically meaningless, construct), this did indeed follow Roff's expectations: the populations that had undergone drift had an average G that was proportional to that of the founding population, as predicted by the theory for a set of replicated populations (i.e., when one actually knows the historical path of evolution). If these results had held for the individual populations that underwent drift, rather than for the statistical construct created by averaging them, this would have been good news indeed. But alas, when Phillips and collaborators examined the Gs of individual populations that had undergone drift, they found that most were not proportional to their control at all: i.e., these matrices appeared to have been produced by selection, not drift, even though there was no significant selection going on! (Pigliucci 2006:16, emphasis in original).

In other words, instances of the evolutionary process don't look like averages over many instances. This is a problem with inferring selection as opposed to drift (i.e., drift in a single population may look like selection), but I would guess there is a corresponding problem inferring drift (i.e., selection in a small sample may look like drift, due to the inaccuracies in estimating covariances). The problem of sample size and covariances is one I may take up again later.

Pigliucci's sixth and final point is that biologists often confuse individual-level versus population-level processes when they talk about "selection on" G matrices. I can see this point, as he describes it:

When considering natural selection, it is clear that physical interactions at the individual level may result in predictable statistical patterns at the population level, and yet this does not imply that the reverse move (from population to individual) is just as straightforward. The point has been made more generally by Shipley (2000), who - in the context of discussing the relationship between causation and correlation in biology - concluded that biologists can test hypothesized causal models by comparing them with their predicted statistical 'shadows,' but cannot reasonably go from the latter to the former. Alas, that is exactly what a great part of the research project in evolutionary quantitative genetics is all about! To put it into another fashion, we can calculate the statistics, but what sort of biological questions are they answering, if any? (Pigliucci 2006:17).

But I'm having trouble thinking of a concrete example that shows why it is a problem, beyond being a conceptual problem.

In any event, that summarizes the critique. It is hard for me to imagine the multivariate study of fossil hominids that answers all these points convincingly. There is maybe some feeling that studies of fossil hominids are imperfect, but will get better if the samples increase in numbers, etc., etc. But Pigliucci has some nice turns of phrase that I like as answers to this idea. For example:

[B]y now it should be clear that quantitative evolutionary biologists ought not to think of these statistical constructs as 'first approximations' to be refined by further research; the difficulty with these constructs is not that they are imprecise (and, therefore, amenable to 'refinement'), but that they do not answer the questions we wish answered (Pigliucci 2006:19).

After his critique, Pigliucci tries to outline ways that might advance our understanding and avoid these conceptual problems. I can't say he has much success at it, since ultimately somebody is going to have to invent new methods to answer the problems.

Additionally, I would say that the problems studying hominid evolution go a lot deeper. Many studies uncritically apply multivariate techniques to samples of five or ten individuals. Keep in mind that these samples are insufficient for estimating variances with reasonable error. Now consider that people are using them to estimate covariances among twenty or more characters. That's a different scale of problem from the ones Pigliucci is describing, but it borders and grades into them.

I do want to quote one part of the conclusion of the paper, because it will be interesting to students of the Fisher-Wright controversy:

The conceptual reason [for commitment to multivariate regression], of more philosophical interest, can be traced back to the rationale that went into the publication of Lande and Arnold's (1983) paper: the main goal there was to provide not just a way to statistically quantify natural selection in action, but to do so while obtaining coefficients of selection that could be directly plugged into the standard quantitative genetics equations for the prediction (or post-diction) of phenotypic evolution. It turns out that, until now, nobody has figured out a way to use path coefficients for the same purpose (but see Scheiner et al. 2000 for the beginning of such an attempt). This implies that a theoretical goal has been for all effective purposes overriding serious conceptual and methodological limitations of the techniques used. What makes this a possible dead end for the entire field is that there are good reasons to believe that the theoretical goal in question - the long-term prediction of evolutionary trajectories - is simply not achievable because of the problems of locality and liability of G discussed above (Pigliucci 2006:20).

That's interesting because, of course, the usual multivariate techniques owe their origin to Fisher, while path analysis was Sewall Wright's solution to some of these genetic problems. Personally, I would say that path analysis is more logical in many ways, but yet it is pretty difficult to implement. A connection between evo-devo genetics and path analysis would be pretty interesting to see.

References:

Pigliucci M. 2006. Genetic variance-covariance matrices: a critique of the evolutionary quantitative genetics research program. Biology and Philosophy 21:1-23. DOI link

Last week's Science has an article about "public acceptance of evolution" by Jon Miller, Eugenie Scott and Shinji Okamoto. The article covers results of polls that demonstrate that a low proportion of Americans believe that humans evolved, compared to relatively higher proportions in Europe and Japan.

Beginning in 1985, national samples of U.S. adults have been asked whether the statement, "Human beings, as we know them, developed from earlier species of animals," is true or false, or whether the respondent is not sure or does not know. We compared the results of these surveys with survey data from nine European countries in 2002, surveys in 32 European countries in 2005, and a national survey in Japan in 2001 (5). Over the past 20 years, the percentage of U.S. adults accepting the idea of evolution has declined from 45% to 40% and the percentage of adults overtly rejecting evolution declined from 48% to 39%. The percentage of adults who were not sure about evolution increased from 7% in 1985 to 21% in 2005. After 20 years of public debate, the public appears to be divided evenly in terms of accepting or rejecting evolution, with about one in five adults still undecided or unaware of the issue. This pattern is consistent with a number of sporadic national newspaper surveys reported in recent years (6-10) (Miller et al. 2006:765).

There's no question that the central point of the article is correct -- a large proportion of Americans reject the idea that evolution explains many of the central facts of life. And I think that Miller, Scott and Okamoto hit upon most of the essential reasons why: the strength of American fundamentalism, the incorporation of creationism into political platforms, and lack of information about "modern genetics". I wonder whether there are additional factors that might be explored, such as a greater skepticism of pronouncements from "experts", or wider awareness of frauds -- side effects of the American political experience and its post-Watergate distrust of authority. But certainly the overwhelming majority of American attitudes toward evolution are influenced by religion, one way or another.

However, I noticed another thing reading this article: just how badly written these poll questions apparently are. Take the one cited above:

"Human beings, as we know them, developed from earlier species of animals."

Human beings have never "developed" from earlier species of animals. We evolved from them. Adult human beings develop from zygotes, embryos, fetuses, infants, children, and adolescents. And of course, some of these latter categories are themselves human beings (teenagers being the main exception!). That's why "evolutionary developmental biology" is called evo-devo instead of devo-devo!

Now, I can understand why a pollster might substitute "developed" for "evolved". "Evolved" is a "charged word", and people might react to it strongly. "Developed" has an everyday meaning that people understand, which isn't necessarily connected to ontogeny.

But really, who exactly is going to "react strongly" to the word evolution, but is going to agree with the notion that human beings developed from earlier species of animals? Somebody who would say, "Oh, well, if we didn't evolve, then I guess I can accept that we developed from monkeys." It's an empty set!

The article presents another set of questions from one of these polls:

For example, only a third of American adults agree that more than half of human genes are identical to those of mice and only 38% of adults recognize that humans have more than half of their genes in common with chimpanzees. In other studies (1, 14, 15), fewer than half of American adults can provide a minimal definition of DNA. Thus, it is not surprising that nearly half of the respondents in 2005 were not sure about the proportion of human genes that overlap with mice or chimpanzees.

Or just maybe, they failed to recognize these "facts" because they are nonsensical!

For example, "more than half of human genes are identical to those of mice"? Let's start by defining some terms. "Identical" generally means "exactly the same". Two identical genes should have the same nucleotide sequence, no? Now, we haven't found all the genes in the human genome. And further, we don't know what segments of DNA should really be included in any given "gene", since each may be regulated by sites that are very far from the coding sequence. So we will want to be very cautious no matter what we claim about similarities between humans and other species.

But let's consider the known coding sequences alone. A sample of some 13,000 genes in the human and draft chimpanzee genomes shows over 39,000 amino-acid coding differences between the two species. This means that a given human will differ from a chimpanzee by an average three amino-acid coding substitutions per gene. Certainly these are not equally distributed -- some genes are more different than others. But far fewer than half of this sample of genes are identical in their amino acid sequences. Even fewer -- only around one in ten -- are identical in their nucleotide sequences, including synonymous substitutions. If we include intronic sequences as part of each gene, then none of the 13,000 genes have identical sequences in humans and chimpanzees. Mice, of course, are more different from us than chimps.

OK, let's be generous and assume that the poll intended something that makes sense, like "more than half of nucleotides are shared between human and chimpanzee genomes." On the one hand, the obtuseness of the question would seem to vindicate those Americans who can't provide "a minimal definition of DNA". I mean, the poll doesn't understand DNA, so why should they?

On the other hand, this looks like what we in the professoriate would call a "trick question". As in:

"Hmm.... The book says that humans and chimpanzees have ninety-eight percent sequence identity, but this question says 'over half'. Now I know that ninety-eight percent is more than half. But why would the question just make up a number that was so far off? Is the question asking about something I didn't study? And it doesn't say 'nucleotide sequence', it says 'genes'. And I know that there aren't any full gene sequences that are identical. And this other question says "in common with." What the hell does that mean? Is it about genes versus pseudogenes? Oh, crap, why didn't I take economics instead?"

Now, sure, there probably aren't very many people who answer these poll questions the "wrong" way because of objections like mine. But when scientists can't seem to get their facts straight, just how exactly are nonscientists supposed to become "literate"?

I actually think 38 percent is pretty impressive penetrance for the human-chimpanzee factoid. After all, only twice that many know that the Earth revolves around the sun.

References:

Miller JD, Scott EC, Okamoto S. 2006. Public acceptance of evolution. Science 313:765-766. DOI link

Did you know that Alan Turing tried to solve the problem of biological form? That following D'Arcy Thompson, he laid the groundwork for an important branch of what has become evo-devo?

Well, Nature News has a story about it, in the context of a bunch of mathematical biologists who have been trying to fit the model to the ontogeny of cat spots:

Turing supposed that coat patterns could be produced by two chemicals, which he called 'morphogens', interacting on the more or less two-dimensional space of the hide. If one morphogen causes hair to turn black, for example, and another causes it to remain pale, then differences in the rates at which these chemicals diffuse through the coat, along with various reactions between the two, would determine the patterns.

Turing called them 'reaction-diffusion equations'. By tweaking the variables of diffusion speed and other behaviours of the morphogens, researchers have been able to use these equations to replicate familiar coat patterns.

For the past couple of decades, people have been trying to fiddle with the parameters of this model to account for various biological patterns, from the positions of leaves on stems of plants to the coat patterns of mammals. The trigger for the story here was the innovation of two distinct stages to account for infant and adult cat coat patterns:

"The pattern of the jaguar was the hardest part," says [researcher Sy-Sang] Liaw, who reports the work in Physical Review E2. "People who try to do the pattern with one stage only will never get it. You have to separate it into two stages."

The interesting part to me is how Turing got interested in the problem. The Slashdot discussion of the topic includes a comment quoting from the topic introduction in the Collected Works of Alan Turing:

For Turing, however, the fundamental problem of biology had always been to account for pattern and form, and the dramatic progress that was being made at that time in genetics did not alter his view. And because he believed that the solution was to be found in physics and chemistry it was to these subjects and the sort of mathematics that could be applied to them that he turned. In my view, he was right, but even someone who disagrees must be impressed by the way in which he went directly to what he saw as the most important problem and set out to attack it with the tools that he judged appropriate to the task, rather than those which were easiest to hand or which others were already using.

You can find one of the relevant papers, "The chemical basis of morphogenesis" at the Turing Archive. Another site has a strangely addictive Java script that yields random biological patterns based on the reaction-diffusion model.

References:

Turing A. 1952. The chemical basis of morphogenesis. Phil Trans Roy Soc Lond B 237:37. Turing Archive

Liu RT, Liaw SS, Maini PK. 2006. Two-stage Turing model for generating pigment patterns on the leopard and the jaguar. Phys Rev E 74:011914. DOI link

This is really cool:

The same genes that give sharks their sixth sense and allow them to detect electrical signals are also responsible for the development of head and facial features in humans, a new study suggests.

The finding supports the idea that the early sea creatures which eventually evolved into humans could also sense electricity before they emerged onto land.

The paper by Renata Freitas and colleagues is in Evolution and Development. Here is the suggestive part of the discussion:

Our finding that the rostral spread of the EphA4 expression domain prefigures the routes taken by mechanosensory and electrosensory axons is reminiscent of mouse ear innervation, in which EphA4 is expressed in the cells lining the auditory nerve pathway, where it directs axons to the cochlea (Pickles 2003). If this function is conserved in the shark laterosensory system, then EphA4 may be involved in guidance of sensory axons to electroreceptors and mechanoreceptors. Indeed, absence of EphA4 expression from ampullary placodes may also relate to the termination of growth cones at these positions. This may be important for both function and development of electroreceptors, as it has been suggested that the arrival of nerve fibers may induce formation of electroreceptive organs (although it is also possible that the placodes attract axons; Fritzsch et al. 1998).

Expression of EphA4 in the shark laterosensory system may represent a deeply conserved mechanism for establishing topographic maps of peripheral sensory inputs in vertebrates. In the mouse, EphA4 and EphrinA5 regulate development of the somatotopic map of projections from sensory whiskers to the barrel fields on the cortex (Vanderhaeghen et al. 2000). EphA4 has been shown to regulate thalamocortical projections, as well as the topographic projections of motor neurons from the spinal cord to the limb (Eberhart et al. 2000, 2002). Similar spatial patterning occurs in the auditory system, where topographic projections originating from the cochlea project to the nucleus magnocellularis, which in turn, innervates the nucleus laminaris in the brain to form a tonotopic map of high- to low-frequency sounds. Interestingly, EphA4 is expressed in a tonotopic gradient at the time when nucleus magnocellularis axons are forming synapses on the nucleus laminaris (Person et al. 2004). The association between expression of EphA4 and development of the shark electrosensory system suggests that EphA4 could play a role in establishing the topographic relationships between peripheral electroreceptors and their primary central targets. Regulation of EphA4 expression during development of the cephalic electrosensory system would therefore underlie how sharks localize the position of electrical stimuli relative to their spatial map of the body. This hypothesis is consistent with EphA4 playing a general role in the establishment of topographic maps during vertebrate embryogenesis (Vanderhaeghen et al. 2000; Yue et al. 2002; Dufour et al. 2003; Person et al. 2004).

This kind of deep genetic homology is not new -- one of the early insights of evo-devo was the widely shared genetic homologies underpinning sight in different lineages who "independently" evolved it. But this is interesting to me because electrosensory organs are easily seen as "exotic" characteristics of some lineages very distant to us. This study suggests that they may have served an important role in the early evolution of tetrapod ancestors. The genes that help generate electroreceptivity in sharks are still expressed in mammals, bent to other purposes.

The LiveScience article has an embryological note of caution from Glenn Northcutt, by the way:

Glenn Northcutt, a neuroscientist at the University of California at San Diego, who was not involved in the study, said the finding was interesting, but that more studies are needed before a direct link between neural crest cells and electroreceptors can be established.

"It still requires a definitive experiment, where the developing neural crest cells are marked with dye, the embryo develops and the dye clearly shows up in the electroreceptors," Northcutt said.

Evolution and Development is a really cool journal. Two of the other articles in the same issue relate to the sensory systems of cave fish -- a classic problem in evolution for which evo-devo approaches are giving interesting answers.

References:

Freitas R, Zhang GJ, Albert JS, Evans DH, Cohn MJ. 2006. Developmental origin of shark electrosensory organs. Evol Devel 8:74. DOI link

Yesterday I ran across this paper by Thomas Flatt in Quarterly Review of Biology, which is a really thorough review of the concept of canalization from its origins to its recent resurgence. Really thorough in this case means that it repeats the same things in several different ways, which is sometimes helpful.

Here's a definition:

Canalization is the reduced sensitivity of a phenotype to changes or perturbations in the underlying genetic and nongenetic factors that determine its expression (see also Meiklejohn and Hartl 2002; De Visser et al. 2003). Canalization is a relative term, and can thus only be defined as a matter of comparison. Thus, a phenotype P is more canalized than another phenotype P* if P remains relatively invariant when the single- or multilocus genotype G, which determines P, is exposed to different environments (environmental canalization) or located in different genetic backgrounds (genetic canalization): P is "resilient," "robust," or "insensitive" to genetic and/or environmental changes or perturbations. Canalization can therefore be recognized by observing that most genetic or environmental changes leave the phenotypic expression of G, and thus the phenotype P, invariant; the expression of G is changed such that specific phenotypic changes (P -> P*) are induced only in some genetic backgrounds or environments (or combinations of genetic backgrounds and environments). Consequently, a canalizing allele or genotype G reduces the phenotypic variation of a trait across a range of genetic backgrounds and environments relative to a noncanalizing allele or genotype G*, and a canalized trait P exhibits a restricted range of phenotypic variation across genetic backgrounds and environments as compared to a noncanalized trait P* (Meiklejohn and Hartl 2002) (Flatt 2005:288).

OK, that's an eyeful. In a nutshell, a more canalized phenotype is one that changes less in response to changes in environment, changes in genetic background, or both.

The definition is complexified by the need to consider behavioral or physiological phenotypes. The paper considers the example of homeotherms, who maintain a single body temperature in a range of environmental ambient temperatures. In this case, the single body temperature is a stable phenotype (upon which much else depends), but it is maintained by diverse physiological mechanisms that are active at different levels and at different times. In this way, canalization is a result of substantial physiological buffering.

Why is canalization important? The intro to the review has this:

Canalization is highly relevant for evolutionary biology. For example, it implies that phenotypes may be stable around their fitness optimum despite genetic and environmental change (e.g., Rendel 1967). By keeping phenotypic variation low, canalization may constrain phenotypic evolution (e.g., Charlesworth et al. 1982; Maynard Smith et al. 1985) and provide a microevolutionary mechanism for character stasis (e.g., Stearns 1994). Canalization also allows genetic variation that is phenotypically not expressed to accumulate. This cryptic variation can lead to the appearance of new phenotypes when development is "decanalized," for instance by environmental stress, thereby allowing evolutionary change (e.g., Rutherford and Lindquist 1998) (Flatt 2005:288).

That is pretty abstract, since it only hints at the adaptive value of canalized phenotypes. What we really would like to know is why some phenotypes would be more canalized than others. The answer could include lots of mechanisms. For one thing, it might be adaptive to have a phenotype that was less vulnerable to environmental modification -- i.e., had less environmental variance. For another as described below, canalization could simply result from the reduction of pleiotropy that results from modularization of genetic or developmental pathways.

Here's one practical application: If you want to find the relationships among a group of species, it is most sensible to choose characters that have a clean distribution of variation --- they should vary relatively little within species, but relatively much between species. Characters that have a great deal of within-species variation are often less useful, because they will often remain polymorphic even within relatively distantly related species.

But a character that has a lot of between-species variation and relatively little within-species variation is exactly the kind of character that may result from canalization. These features may reflect adaptive canalization that differs among a group of species; they may reflect some kinds of developmental constraints on one or more developmental modules. In any event, we should be aware that the kinds of characters that tend to be most useful for phylogenetic reconstruction will have certain evolutionary characteristics.

This section is relevant to me, so I'm including it:

Modularity of development may contribute to canalization (Stearns 1989b; Maynard Smith 1998; Hartwell et al. 1999; Stern 2000). Changes in the organism in one of its parts should not compromise other achievements: independent functions should be coded independently so that the change of one function does not interfere with other optimized functions (G P Wagner and Altenberg 1996). Modularity can be a way to achieve this independence of functions. The significance of modularity for canalization is that perturbing one module does not necessarily perturb the development of the whole organism: the embedding of particular functions into distinct modules allows for phenotypic change by altering connections among the modules while the core function of a given module remains unchanged (G P Wagner and Altenberg 1996; Hartwell 1999; Stern 2000; Schank and Wimsatt 2001). First, if deleterious mutations are highly pleiotropic (but see Stern 2000), then these mutations are likely to have a negative effect on many traits. If gene networks have a modular structure, however, then genetic change in one of the modules does not necessarily influence the others (Bonner 1988). Thus, by restricting pleiotropy, modularity allows some modules to continue to function when others change (Schank and Wimsatt 2001). Second, random mutations of a given phenotypic effect are likely to be more deleterious in complex organisms consisting of many traits as compared to simpler organisms with less traits (Fisher 1930; Orr 2000). Fisher (1930) suggested that mutations of small phenotypic effect are more likely to be favorable than mutations with large effects. In a topological model, he showed that the probability of approaching (or deviating from) the fitness optimum is higher (or smaller) if a mutation has a small phenotypic effect than if it has a large phenotypic effect. In the latter case, a mutation is more likely to go beyond the optimum or to deviate from it more strongly than if the mutation has only a small phenotypic effect. For the same intuitive reason, random mutations of a given phenotypic effect are more likely to disrupt a complex than a simple organism (Orr 2000). It would therefore be evolutionarily advantageous to reduce the number of independent traits by bundling them into modules (Orr 2000) (Flatt 2005:299-300).

The review does not link this topic of modularity and canalization to evo-devo, but it seems like a fertile topic to me. The presence of different canalized pathways that might be alternated by genetic switches of various kinds is also a very interesting topic.

References:

Flatt T. 2005. The evolutionary genetics of canalization. Q Rev Biol 80:287-316. Full text (subscription).

On the Scientific American website, there is a long article by Michael Shermer (editor of Skeptic magazine), describing his trip to the World Summit of Evolution, held in the Galapagos Islands this month. Some of the attendees:

It was a veritable Who's Who of evolutionary theory, including William Calvin, Daniel Dennett, Niles Eldredge, Douglas Futuyma, Peter and Rosemary Grant, Antonio Lazcano, Lynn Margulis, William Provine, William Schopf, Frank Sulloway, Timothy White and others.

Shermer provides a rundown of many of the scientific presentations, and it is an interesting read. The paleoanthropology representative was Tim White, and Shermer gives him almost a whole page:

One of the best talks of the conference was delivered by the U.C. Berkeley paleoanthropologist Timothy White, in which he opened with a prediction made by Stephen Jay Gould in the late 1980s: "We know about three coexisting branches of the human bush. I will be surprised if twice as many more are not discovered before the end of the century." A glance at the extant fossil record looks like Gould was right. There are at least two dozen fossil species in six million years of hominid evolution. But the bush is not so bushy, says White. The problem lies in the difference between "lumpers" and "splitters" in species classification, and the social pressures to publish extraordinary new discoveries. If you want to get your fossil find published in Science or Nature, and you want the cover illustration, you cannot conclude that your fossil is yet another Australopithicus africanus [sic], for example. You better come up with an interpretation indicating that this new find you are revealing for the first time to the world is the most spectacular discovery of the last century and that it promises to overturn hominid phylogeny and send everyone back to the drawing board to reconfigure the human evolutionary tree. Training a more skeptical eye on many of these fossils, however, shows that many, if not most of these fossils belong in already well-established categories. White says that the specimen labeled Kenyanthropus platyops, for example, is very fragmented and is most likely just another Australopithicus africanus [sic]. "Name diversity does not equal biological diversity," White elucidated.

If I had a quote list, I'd add that one to it: "Name diversity does not equal biological diversity." On the other hand, White has himself had the cover of Nature once or twice....

And then there is this:

White then concluded his talk with a fascinating discussion of the recent discovery of fossil dwarf humans on Flores Island in the Malay Archipelago, located on the outside of Wallace's Line, meaning that even during the last ice age they could only have gotten there by boat. (White did note, however, that after last December's tsunami people were rescued from large floating rafts of natural debris, so it is possible that the founding population of Flores rafted there by accident and not design.) ... A second published specimen put to rest the pathology hypothesis that Homo floresensis was a microcephalic human. The best evidence, says White, points to insular dwarfing, a rapid punctuation event out of Homo sapiens that led to a shrinkage of these isolated people. Such dwarfing effects can be seen on this and other islands, where large mammals get smaller (like the dwarf elephant), and small reptiles get larger (like the Komodo Dragon). The chances of any living members of this species still existing in the hinterlands of Flores are extremely remote, but some observers have noted that the indigenous peoples of Flores recount a myth of small hairy humans who descend from the highlands to steal food and supplies.

You can read what I have to say about Homo floresiensis here. I'm telling you, the more this story gets repeated, the worse it's going to turn out.

Most of the meeting was relatively big-name evolutionary biologists of one kind or another. In the end, it sounds to me like the many of the invitees wanted to trash Darwinism to promote their own idiosyncratic theories. To some extent, Shermer displays his best skeptical take on these, although he describes one as "beyond [his] pay scale." A lot of famous scientists have problems with standard neo-Darwinism, and it seems that many were invited to this meeting, with very few representatives of the more standard point of view. So Shermer's article includes many "proclaiming the death of Darwin" stories. Interesting in this context that there appear to have been no evo-devo people at the conference, since this is probably the most important of the extensions to evolutionary theory, and one that resonates with pre-Darwinian biology to a much greater extent than ideas like Margulis' pansymbiosis or multilevel selection theory.

Read the article and see if you agree with Shermer that evolutionary biology is in a healthy state. My take is that a show of real health would have included a slightly different list of biologists.

The following quote really sums up the problem with "intelligent design" as science, and why it is not taken seriously. It comes from a review by Alan D. Gishlick of Jonathan Wells' Icons of Evolution on the National Center for Science Education website.

When Alfred Wegener first proposed his theory of continental drift, he was laughed at and ridiculed. What did he do? Did he form a non-profit advocacy group and lobby state school boards and lawmakers to force teaching of "evidence against" geosynclinal theory? Write a book called Icons of Uniformitarianism? Evaluate and grade earth science textbooks and demand that they be rewritten to remove examples of "borderlands"? No. He went back and did more research. He found like-minded colleagues and they produced research. He fought in the peer-reviewed literature. He produced original research, not polemical popular tracts or politics. Eventually his ideas were adopted by the whole of geology -- not through politics but because of their overall explanatory power. If [Jonathan] Wells and his colleagues [in the ID movement] want "intelligent design" to succeed, they need to produce that research.

I like this because it appeals to the real spirit of scientific progress. If you want other people to believe your theory, then get to work! Test it against real evidence. Face the evidence, not your critics. This is the Internet Age, people, and making up stories about other peoples' work won't pass the Google test.

The thread is picked up by Paul Z. Myers, writing in the Minneapolis Star-Tribune (I also link to his weblog version, since the Star-Tribune's articles are not