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.

Castrating trematodes!

Since I mentioned yesterday that penis size mattered, upon stumbling on this article about the horrific effects of a trematode infestation, I thought everyone might enjoy a grim and vivid picture of what trematodes can do to a poor, innocent mollusc.

This is a photo of a trematode, or fluke. Trematodes are parasitic flatworms with very complex life cycles; this particular one is a cercaria, or tailed larva. They swim about and infest various hosts at various stages, proliferating and spreading through tissues, before moving on to infect the next host in their cycle.

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Male enhancement works!

I hate those commercials on cable TV for Enz*te, that fake “male enhancement” product that promises a “boost of confidence” for all the guys who take their little pill. I don’t believe it, of course—it’s probably a concoction of sawdust and rat droppings. But the phenomenon of male confidence as a function of the size of their physical attributes might just have some validity.

AL Basolo, who did some well-known work on mate preference in swordtails a few years ago (short answer: lady swordtails prefer males with longer swords), has a couple of new papers on the subject. She has looked at competition between males—the fishy equivalent of checking out the other guy’s equipment in the lockerroom—and found that the length of the sword makes a big difference in the struggle between males, even with no females involved.

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Xiphophorus helleri is a common aquarium fish with a distinctive feature: that long sword on its tail. The males have competitive interactions with each other that are fairly easy to assess: dominant males chase away inferiors, and inferiors avoid the winners, so you just have to record who is chasing who to sort out who thinks they are in charge. Usually, it’s the fish that is bigger overall that wins. The investigators suspected that the size of the sword might also be a deciding factor. Observations of pairs of fish matched for body size, but with natural differences in sword length, did not bear this out, however, showing little correlation. That suggests, as one might expect, that there are multiple factors that influence competitions.

To simplify those factors, they carried out what sounds to me like a very cruel experiment. Pairs of fish matched for body size were anesthetized, their swords chopped off, and replaced with transparent plastic swords of identical size. The difference, though, was that different length swords were painted on the transparent plastic—one lucky fish got a new painted sword roughly the same length as the old one, while the other got a sword half the length.

After recovering from their implant surgery, they were put together in a tank…and the truncated male consistently lost all competitions. I guess size matters, after all.

Without the gross surgical modifications, however, size wasn’t such a clear indicator of victory, so other factors must also play a role. A companion paper looked at stripes on the sword, and how they affected female interests. This work modified the tails digitally; a video recording of a hunky male was made, and then edited to either remove the stripes from its entire length, to remove them from the proximal half or the distal half, or left intact. The video was played back to a female, and the length of time she paid attention to it measured (longer is better).

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Female response to the four male video stimuli (pictured above each bar from left to right: complete sword, distal stripes, proximal stripes, no stripes). Bars with the same colour pattern did not differ significantly.

The lessons are clear. Having a long sword will help you intimidate and beat up your competition, and painting stripes along its length (or at least at the tip) will win you the admiration of females.

If you’re a fish, that is.

There is no necessary expectation that it will help at all if you’re a hairless ape, but if anyone tries it, let me know how it turns out.

Benson KE, Basolo AL (2006) Male–male competition and the sword in male swordtails, Xiphophorus helleri. Animal Behaviour 71(1):129-134.

Trainor BC, Basolo AL (2006) Location, location, location: stripe position effects on female sword preference. Animal Behaviour 71(1):135-140.

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.

Where are the spineless?

Hey! I’m supposed to host the Circus of the Spineless next week (I think on 29 January), and I’ve only received one submission so far! Someone must have written something somewhere about invertebrates, right? There is a set of rules for submissions, but it’s going to be simple: I’ll accept anything about any organisms outside the class Vertebrata.

I’ll spell it out. You can write about the phyla Acanthocephala, Acoelomorpha, Annelida, Arthropoda, Brachiopoda, Bryozoa, Chaetognatha, Cnidaria, Ctenophora, Cycliophora, Echinodermata, Echiura, Entoprocta, Gastrotricha, Gnathostomulida, Hemichordata, Kinorhyncha, Loricifera, Micrognathozoa, Mollusca, Myxozoa, Nematoda, Nematomorpha, Nemertea, Onychophora, Orthonectida, Phoronida, Placozoa, Platyhelminthes, Pogonophora, Porifera, Priapulida, Rhombozoa, Rotifera, Sipuncula, Symplasma, or Tardigrada, and that’s fine. You can even write about the Urochordata, the Cephalochordata, and the Myxini within the phylum Chordata. The overwhelming majority of animal species are fair game, so there is absolutely no excuse if anyone tries to send me a picture of their cat. Understand? Fish, frogs, lizards, birds, mammals, dinosaurs, and your baby pictures are right out.

I’m also going to accept multiple submissions, if you’ve been manic about documenting the breadth of biodiversity. We shall do our best to overcome the bias of the blogosphere for kitties and other furred and feathered and scaled beasties.

Although the tagline for the circus says it is a monthly celebration of “most anything else that wiggles”, I’m also going to break the shackles of metazoan chauvinism, so if you want to send in something about protists, lichens, fungi, plants, whatever, anything but things with a spinal column, I’ll accept them and put them in an honored category of their own.

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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