Life is chemistry

Sometimes creationists say things like, “Evolution doesn’t explain the origins of life!” The common reply is that that’s the domain of abiogenesis, not evolution, with the implied suggestion that the creationist should go away and quit bugging us.

That’s a cop-out.

I’m going to be somewhat heretical, and suggest that abiogenesis as the study of chemical evolution is a natural subset of evolutionary theory, and that we should own up to it. It’s natural processes all the way back, baby, no miracles required. Life is chemistry, vitalism has evaporated and is one with phlogiston, and scientists legitimately and respectably study physical processes that were the potential instigators of life. Someday we’re going to be able to create living cells from scratch, and those mechanisms will be taken for granted afterwards, just as Wöhler’s synthesis of urea is nowadays.

What prompts this assertion of uncompromising naturalism is a reminder from two publications. Natural History has published a nice review of The Origins of Life, and The Scientist has an article on the work to create a synthetic cell, Is This Life?. They’re both good, light summaries that don’t stint on pointing out the problems in these fields—but the main point is that there has been great progress as well, and that these are productive lines of inquiry.

Vertebral variation, Hox genes, development, and cancer

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First, a tiny bit of quantitative morphological data you can find in just about any comparative anatomy text:

mammal number of vertebrae
cervical thoracic lumbar sacral caudal
horse 7 18 6 5 15-21
cow 7 13 6 5 18-20
sheep 7 13 6-7 4 16-18
pig 7 14-15 6-7 4 20-23
dog 7 13 7 3 20-23
human 7 12 5 5 3-4

The number of thoracic vertebrae varies quite a bit, from 9 in a species
of whale to 25 in sloths. The numbers of lumbar, sacral, and more caudal vertebrae also show considerable variation. At the same time, there is a surprising amount of invariance in the number of cervical vertebrae in mammals — as every schoolkid knows, even giraffes have exactly the same number of vertebrae in their necks as we do. What makes this particularly striking is that other vertebrates have much more freedom in their number of cervical vertebrae; swans can have 22-25. I was idly wondering why mammals were so limited, and stumbled onto a couple of papers that addressed exactly that question (Galis & Metz, 2003; Galis, 1999). Galis’s explanation is that it is a developmental constraint that may have something to do with the incidence of cancer.

Development is an intricately choreographed process that treads a dangerous line. On one side is stability; but development is in many ways a destabilizing process, in which cells have to change their path and form new tissues, and stability is not compatible with it. On the other side is chaos, unregulated proliferation — cancer. During development, the organism has to foster proliferation and change to a greater degree than it can tolerate later, and that loosening of constraints represents a danger. Galis suggests that one reason we mammals may always have 7 cervical vertebrae is that the regulatory genes that specify the number of vertebrae are coupled to processes that otherwise regulate cell fates, and that modifications to those genes that would cause variation in vertebra number would also lead to unacceptable increases in the frequency of embryonal cancers.

This isn’t at all an improbable idea. Genes exhibit bewilderingly complex patterns of expression, and pleiotropy (the regulation of multiple phenotypic characters by a single gene) is the rule, not the exception. The Hox genes, the particular genes that control the identity of regions along the length of the animal, are known to switch on and off in proliferating mammalian cell lines in culture. Perhaps the Hox genes involved in defining cervical vertebrae are somehow also involved in controlling cell proliferation, making them dangerous targets for evolution to tinker with?

Galis provides several lines of evidence that this is the case. To see whether variation in cervical vertebra number leads to increased incidence of cancer, we need to look for instances of variation in mammalian vertebrae.

There isn’t much variation in cervical vertebra number, though. There is an exception: sometimes, the 7th cervical vertebra is found to undergo a partial homeotic transformation and forms a pair of ribs, which are normally found only on thoracic vertebrae. Humans develop cervical ribs with a frequency of about 0.2%; do they also develop cancers? The answer is yes, with a frequency 125 times greater than the general population.

Another place to look would be in phylogenetic variation — between groups rather than within a population. It turns out that there are two groups of mammals that do have a non-canonical number of cervical vertebrae: one manatee genus and two genera of sloths. No data is available on frequencies of embryonal cancers in either, and Galis reports that manatees at least seem to have a low incidence of cancer. One explanation is that both sloths and manatees have exceptionally slow metabolic rates, which in itself will reduce the frequency of cancer, since it will reduce the rate of oxidation damage; the idea is that this low cancer rate may have made these organisms more tolerant of variation in these genes.

An open question is how birds can have greater variability in the number of cervical vertebrae — they certainly don’t have low metabolic rates. One suggestion is that the coupling between these particular Hox genes and a predilection for cancer is unique to mammals. Another possibility is that birds possess other, unidentified mechanisms that reduce free radical production, reduces oxidative damage, and makes them relatively cancer-free. Galis cites several studies that show that birds do seem to be less severely afflicted with cancers than us mammals.

It’s an interesting idea, but the evidence so far is a collection of correlations. I’d be interested in seeing some direct analyses of the role of patterning genes on carcinogenesis. Still, it’s the first answer I’ve seen to explain why such a peculiar restriction in morphology should be nearly universal within a whole class of animals, when other classes allow so much more diversity.

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Galis, F and JAJ Metz (2003) Anti-cancer selection as a source of developmental and evolutionary constraints. BioEssays 25:1035-1039.

Galis, F (1999) Why do almost all mammals have seven cervical vertebrae? Developmental constraints, Hox genes, and cancer. J Exp Zool (Mol Dev Evol) 285:19-26.

A rising starlet in evo-devo

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Nematostella, the starlet anemone, is a nifty new model system for evo-devo work that I’ve mentioned a few times before—in articles on “Bilateral symmetry in a sea anemone” and “A complex regulatory network in a diploblast”—and now I see that there is a website dedicated to the starlet anemone and a genomics database, StellaBase. It’s taking off!


Two legged goats and developmental variation

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Variation is common, and often lingers in places where it is unexpected. The drawing to the left is from West-Eberhard’s Developmental Plasticity and Evolution(amzn/b&n/abe/pwll), and illustrates six common variations in the branching pattern of the aortic arch in humans. These are differences that have no known significance to our lives, and aren’t even visible except in the hopefully rare situations in which a surgeon opens our chests.

This is the kind of phenomenon in which I’ve become increasingly interested. I work with a model system, the zebrafish, and supposedly one of the things we model systems people pursue is the ideal of a consistent organism, in which the variables are reduced to a minimum. Variation is noise that interferes with our perception of common underlying mechanisms. I’ve been thinking more and more that variation is actually a significant phenomenon that tells us something about where the real constraints in the system are. It is also, of course, the raw material for evolution.

Unfortunately, variation is also relatively difficult to study.



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I’m redundant-who needs a blogger?

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There’s a lovely article in this week’s Nature documenting a transitional stage in tetrapod evolution (you know, those forms the creationists like to say don’t exist), and a) Nature provides a publicly accessible review of the finding, and b) the primary author is already a weblogger! Perhaps there will come a day when I’m obsolete and willl just have to turn my hand to blogging about what I had for lunch.

For an extra super-duper dose of delicious comeuppance, though, take a look at this thread on the Panda’s Thumb. I wrote about Panderichthys, and a creationist (“Ghost of Paley”) comes along to mangle the phylogeny and make wild negative assertions about the validity of interpretations of fossils based on work from the Ahlberg lab…when Martin Brazeau of the Ahlberg lab and author of this new paper shows up to straighten him out.

And for my next trick, let me introduce you to Marshall McLuhan…

Brazeau MD, Ahlberg PE (2006) Tetrapod-like middle ear architecture in a Devonian fish. Nature 439:318-321.

Deficiencies in modern evolutionary theory

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This is a post originally made on the old Pharyngula website; I’ll be reposting some of these now and then to bring them aboard the new site.

There are a number of reasons why the current theory of evolution should be regarded as incomplete. The central one is that while “nothing in biology makes sense except in the light of evolution”, some important disciplines within biology, development and physiology, have only been weakly integrated into the theory.

Raff (1996) in his book The Shape of Life(amzn/b&n/abe/pwll) gives some of the historical reasons for the divorce of evolution and development. One is that embryologists were badly burned in the late 19th century by Haeckel, who led them along the long and unproductive detour of the false biogenetic “law”. That was a negative reaction; there was also a positive stimulus, the incentive of Roux’s new Entwicklungsmechanik, a model of experimental study of development that focused exclusively on immediate and proximate causes and effects. Embryology had a Golden Age of experimentation that discouraged any speculation about ultimate causes that just happened to coincide with the time that the Neo-Darwinian Synthesis was being formulated. Another unfortunate instance of focusing at cross-purposes was that the Neo-Darwinian Synthesis was fueled by the incorporation of genetics into evolutionary biology…and at the time, developmental biologists had only the vaguest ideas about how the phenomena they were studying were connected to the genome. It was going to be another 50 years before developmental biology fully embraced genetics.

The evolutionary biologists dismissed the embryologists as irrelevant to the field; furthermore, one of the rare embryologists who tried to address evolutionary concerns, Richard Goldschmidt, was derided as little more than a crackpot. It’s an attitude that persists today. Of course, the problem is mutual: Raff mentions how often he sees talks in developmental genetics that end with a single slide to discuss evolutionary implications, which usually consist of nothing but a sequence comparison between a couple of species. Evolution is richer than that, just as development is much more complex and sophisticated than the irrelevant pigeonhole into which it is squeezed.

In her book, Developmental Plasticity and Evolution(amzn/b&n/abe/pwll), West-Eberhard (2003) titles her first chapter “Gaps and Inconsistencies in Modern Evolutionary Thought”. It summarizes the case she makes in the rest of her 700 page book in 20 pages; I’ll summarize her summary here, and do it even less justice.

She lists 6 general problems in evolutionary biology that could be corrected with a better assimilation of modern developmental biology.

  1. The problem of unimodal adaptation. You can see this in any textbook of population genetics: the effect of selection is to impose a gradual shift in the mode of a pattern of continuous variation. Stabilizing selection chops off both tails of the distribution, directional selection works against one or the other tail, and disruptive selection favors the extremes. This is a useful, productive simplification, but it ignores too much. Organisms are capable of changing their specializations either physiologically, in the form of different behaviors, morphologies, or functional states, developmentally in the form of changing life histories, or behaviorally. Evolution is too often a “theory of adults”, and rather unrealistically inflexible adults at that.
  2. Cohesiveness. There is a long-standing bias in the evolutionary view of development, that of development imposing constraints on the organism. We can see that in the early favor of ideas like canalization, and the later vision of the gene pool as being cohesive and coadapted, which limits the magnitude of change that can be permitted. It’s a view of development as an exclusively conservative force. This is not how modern developmental biologists view the process. The emerging picture is one of flexibility, plasticity, and modularity, where development is an innovative force. Change in developmental genes isn’t destructive—one of the properties of developmental systems is that they readily accommodate novelty.
  3. Proximate and ultimate causation. One of the radical secrets of Darwin’s success was the abstraction of the process away from a remote and unaccessible ultimate teleological cause and to a more approachable set of proximate causes. This has been a good strategy for science in general, and has long been one of the mantras of evolutionary biology. Organisms are selected in the here and now, and not for some advantage many generations down the line. Evolutionary biology seems to have a blind spot, though. The most proximate features that affect the fitness of an organism are a) behavioral, b) physiological, and c) developmental. These are the causes upon which selection can act, yet the focus in evolutionary biology has been on an abstraction at least once removed, genetics.
  4. Continuous vs. discrete change. This is an old problem, and one that had to be resolved in a somewhat unsatisfactory manner in order for Mendelian genetics (an inherently discrete process) to be incorporated into neo-Darwinian thought (where gradualism was all). Many traits can be dealt with effectively by quantitative genetics, and are expressed in a graded form within populations, and these are typically the subject of study by population geneticists. We often see studies of graded phenotypes where we blithely accept that these are driven by underlying sets of graded distributions of genes, such as the studies of Darwin’s finches by the Grants, yet those genes are unidentified. Conversely, the characters that taxonomists use to distinguish species are usually qualitatively distinct are at least abruptly discontinuous. There is a gap in our thinking about these things, a gap that really requires developmental biology. Wouldn’t it be useful to know the molecular mechanisms that regulate beak size in Darwin’s finches?
  5. Problematic metaphors. One painful thing for developmental biologists reading the literature of evolutionary biology is the way development is often reduced to a metaphor, and usually it is a metaphor that minimizes the role of development. West-Eberhard discusses the familiar model of the “epigenetic landscape” by Waddington, which portrays development as a set of grooves worn in a flat table, with the organism as a billiard ball rolling down the deepest series. This is a model that completely obliterates the dynamism inherent in development. Even worse, because it is the current metaphor that seems to have utterly conquered the imaginations of most molecular biologists, is the notion of the “genetic program”. Again, this cripples our view of development by removing the dynamic and replacing it with instructions that are fixed in the genome. This is bad developmental biology, and as we get a clearer picture of the actual contents of the genome, it is becoming obviously bad molecular biology as well.
  6. The genotype-phenotype problem. Listen to how evolutionary explanations are given: they are almost always expressed in the language of genes. Genes, however, are a distant secondary or tertiary cause of evolutionary solutions. Fitness is a collective product of success at different stages of development, of different physiological adaptations, and of extremely labile interactions with the environment. Additionally, a gene alone is rarely traceable as the source of an adaptive state; epigenetic interactions are paramount. We are rarely going to be able to find that a specific allele has a discrete adaptive value. It’s always going to be an allele in a particular genetic background in a particular environment with a particular pattern of expression at particular stages of the life history.

One unfortunate problem with discussing these issues in venues frequented by lay people is, you guessed it, creationism. Any criticism of a theory is seized upon as evidence that the theory is wrong, rather than as a sign of a healthy, growing theory. The Neo-Darwinian Synthesis is not wrong, but neither is it dogma. It was set up roughly 70 years ago with the knowledge that was available at the time, and it is not at all surprising that the explosion of new knowledge, especially in molecular biology, genetics, and developmental biology, means that there are radically different new ideas clamoring to be accommodated in the old framework. The theory is going to change. This isn’t cause for creationists to rejoice, though, because the way it is changing is to become stronger.

Orsten fossils

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Bredocaris admirabilis

Ooooh, there’s a gorgeous gallery of Orsten fossils online. These are some very pretty SEMs of tiny Cambrian animals, preserved in a kind of rock called Orsten, or stinkstone (apparently, the high sulfur content of the rock makes it smell awful). What are Orsten fossils?

Orsten fossils in the strict sense are spectacular minute secondarily phosphatised (apatitic) fossils, among them many Crustacea of different evolutionary levels, but also other arthropods and nemathelminths. The largest fragments we have do not exceed two mm. Orsten-type fossils, on the other hand, have the great advantage in being three-dimensionally preserved with all surface structures in place and thus easier to interpret than any other fossil material. Orsten fossils are preserved virtually as if they were just critical-point dried extant organisms. Details observable range down to less than 1 µm, and include pores, sensilla and minute secondary bristles on filter setae and denticles. Orsten fossils also give an insight of meiofaunal benthic life at small scale, including preservation larval stages, and hence a life zone inhabited by the earliest metazoan elements of the food chain.

It’s a good browse over there. I think it’s useful to remember that the majority of the fauna of the world both extant and half a billion years ago is and was tiny and unfamiliar.

Hemichordate evo-devo

Every biology student gets introduced to the chordates with a list of their distinctive characteristics: they have a notochord, a dorsal hollow nerve cord, gill slits, and a post-anal tail. The embryonic stage in which we express all of these features is called the pharyngula stage—it’s often also the only stage at which we have them. We terrestrial vertebrates seal off those pharyngeal openings as we develop, while sea squirts throw away their brains as an adult.

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The chordate phylum has all four of those traits, but there is another extremely interesting phylum that has some of them, the hemichordates. The hemichordates are marine worms that have gill slits and a stub of a tail. They also have a bundle of nerves in the right place to be a dorsal nerve cord, but the latest analyses suggest that it’s not discrete enough to count—they have more of a diffuse nerve net than an actual central nervous system. They don’t really have a notochord, but they do have a stiff array of cells in their proboscis that vaguely resembles one. They really are “half a chordate” in that they only partially express characters that are defining elements of the chordate body plan. Of course, they also have a unique body plan of their own, and are quite lovely animals in their own right. They are a sister phylum to the chordates, and the similarities and differences between us tell us something about our last common ancestor, the ur-deuterostome.

Analyzing morphology is one approach, but this is the age of molecular biology, so digging deeper and comparing genes gives us a sharper picture of relationships. This is also the early days of evo-devo, and an even more revealing way to examine related phyla is to look at patterns of gene regulation—how those genes are turned on and off in space and time during the development of the organism—and see how those relate. Gerhart, Lowe, and Kirschner have done just that in hemichordates, and have results that strengthen the affinities between chordates and hemichordates. (By the way, Gerhart and Kirschner also have a new book out, The Plausibility of Life (amzn/b&n/abe/pwll), which I’ll review as soon as I get the time to finish it.)

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