A Pain in the Neck: Homeosis in Sloths and Manatees
Many people have heard the fascinating factoid that the comically elongated necks of giraffes actually comprise the same number of cervical (neck) vertebrae as humans, and it’s absolutely true—the giraffe’s neck vertebrae are each stretched out to nearly 10 inches long to achieve such a feat. The similarity isn’t limited to our species and giraffes: nearly all mammals, from bats to bonobos, have exactly 7 cervical vertebrae, a staunch testament to their shared ancestry.
Because nature invariably keps things interesting for us, however, there is an exception to the rule. Apparently sloths (both the 2 toed, Choelopus, and 3-toed, Bradypus ) and manatees ( Trichechus ) are the two known taxa that break the Rule of 7 Mammalian Cervicals. How and why? A study by Varela-Lasheras et al. (2011) in a recent issue of the journal EvoDevo tackled these questions, investigating exactly how these species managed to break the pattern that is so consistent across such a diverse and comprehensive range of other mammals.
There have been two primary competing hypotheses as to how these aberrant neck constructions came to be:
1) Homeotic Transformation: Mammalian vertebrae are differentiated into four regions: the cervical, thoracic, and lumbar segments of the spine, plus the sacrum (basically a fusion of the posterior vertebrae that formed the tail in our ancestors), and during our development the differentiation of these vertebrae is controlled by Hox genes. Thus, a homeotic transformation (also known as homeosis) is what happens when one of those developmental genes is mutated or expressed abnormally, often resulting in what should have been one body part developing into a different one. For example, if the gene called Antennapedia in flies does not function correctly, an extra pair of legs will grow where the antennae should have been.. In this line of thought, the abnormal number of cervical vertebrae in sloths and manatees results from a disruption in normal function of these Hox genes controlling segmentation, creating abnormalities in the usual differentiation of the mammalian spinal regions. Mutations such as these are often pleiotropic, meaning change in a single gene can cause multiple abnormalities. Some conditions associated with spinal homeosis include cryptochridism and sterility (Rijli et al. 1995), malformation and asymmetry of other skeletal structures (Charite et al.1994) and increased cancer risk (Schumacher et al. 1992).
2) Alteration in primaxial/abaxial patterning: Advocated by Bucholtz and Stepien (2009), this hypothesis claims that there are not actually more cervical vertebrae, there are simply more thoracic vertebra without attached ribs, which are being mistaken for extra cervicals. (This is the opposite of what happens in Cervical Rib Syndrome, sometimes seen in about 0.5% of humans, in which the last cervical has a supernumerary rib-like projection, which can cause issues compression of critical arteries, nerves and musculature).
The new study by Varela-Lasheras et al. sought to determine which of these hypotheses is the accurate explanation for vertebral patterns seen in sloths and manatees. To do this, the researchers carefully studied the skeletal characteristics of these and members of related taxa with mutations causing abnormal vertebral patterns. After extensive comparative analyses, they showed that sloths and manatees do show many of the skeletal malformations that are common to other species with Hox mutations, including transgenic lab mice with engineered Hox dysfunctions. All of this serves as strong support for the homeosis hypothesis over the primaxial/abaxial approach.
These results bring us to a significant question: why is it that sloths and manatees have been able to soldier on through the generations carrying a high load of Hox-related pleiotropic malformations, whilst the same mutations appear to have been consistently selected against in all other mammal species?
The authors attribute the weak selection against homeosis in sloths and manatees to their infamously low metabolisms:
“The weak selection is probably due to a lower
number and lower harmfulness of pleiotropic effects, both related to the extremely
low activity and metabolic rates. Low activity is expected to minimize the
harmfulness of skeletal and other anatomical abnormalities, and hence, lowers the
biomechanical constraint on changes of the number of cervical vertebrae. Low
metabolic rates are expected to reduce the harmfulness of pleiotropic effects, in
particular by reducing the incidence and severity of cancer and other free radical
Fascinating study, and it will be interesting to see if, in the future, any other species are found to show similarly divergent patterns from the what is an almost (yet not quite, obviously) universal blueprint for the mammalian spinal column. Marsupials are known to have basal metabolic rates about 30% lower than eutherians, on average (Dawson and Hulbert 1970), so it would be fascinating to see if they also show higher tolerance for structural “abnormalities” as compared to their placental counterparts, especially considering that the koala ( Phascolarctos cinereus ) has a lifestyle broadly comparable to that of the sloths. It will be interesting to keep up with new developments in this line of research!
Varela-Lasheras, I., Bakker, A., van der Mije, S., Metz, J., van Alphen, J., & Galis, F. (2011). Breaking evolutionary and pleiotropic constraints in mammals. On sloths, manatees and homeotic mutations. EvoDevo, 2 (1) DOI: 10.1186/2041-9139-2-11
Buchholtz, E. A. and C. C. Stepien. 2009. Anatomical transformation in mammals:
developmental origin of aberrant cervical anatomy in tree sloths. Evol Dev 11: 69-7.
Charite, J., W. de Graaff, S. Shen, J. Deschamps. 1994. Ectopic expression of Hoxb-8 causes duplication of the ZPA in the forelimb and homeotic transformation of axial structures. Cell 78: 589-601.
Dawson, T. J. and A. J. Hulbert. 1970. Standard metabolism, body temperature, and surface areas of Australian marsupials. _ American Journal of Physiology_ 218: 1233-1238.
Rijli, F. M., R. Matyas, M. Pellegrini, A. Dierich, P. Gruss, P. Dolle, and P. Chambon. 1995 Cryptorchidism and homeotic transformations of spinal nerve and vertebrae in Hoxa-10 mutant mice. Proc. Natl. Acad. Sci. USA 92: 8185-8189.
Schumacher R, Mai A, Gutjahr P: Association of rib anomalies and malignancy
in childhood. Eur J Pediatr 1992, 151: 432-434
Antennapedia and sloth images courtesy of WikiCommons, spinal diagram source here.