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

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 7^th 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.

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.

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!

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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