Switching off for winter is not easy. Only a select few species dramatically reduce their metabolism and hibernate to endure the long dark months, and how this remarkable tactic came about is not clear. ‘The evolutionary origin [of hibernation] is completely unknown’, says William Wong from Johns Hopkins University School of Medicine, USA. According to Wong, a team lead by Noriaki Kondo from the Kanagawa Academy of Science and Technology, Japan, discovered a protein complex – hibernation protein (HP) complex – in 1992 that was present in the genomes of hibernating squirrel species, such as chipmunks, but absent in non-hibernating squirrel species. ‘This implies the acquisition of unique genes in the course of evolution that enables mammals to hibernate’, says Wong. However, it wasn't clear whether the presence of this complex was restricted to hibernators. Could the complex turn up in the DNA of non-hibernating mammals too? ‘Given that the genomes of many mammals have been sequenced, we decided to see if HP complex is indeed unique to the hibernators’, says Wong (p. 2667).

However, when Wong and his colleagues searched the genomes of non-hibernating mammals, from the nine-banded armadillo and European rabbit to the bottlenosed dolphin, cow, pig and elephant, they were astonished to find that all of the genes that encode the HP complex were also present in the genomes of these animals. In addition, they found that the HP genes occurred in the same locations in the genomes of non-hibernators as they did in the hibernators' genomes. So, the genes had been conserved during evolution even though none of the species under investigation were hibernators, but how were the genes functioning in the non-hibernators? Maybe there was something different about the way that the genes were expressed to prevent the non-hibernators from hibernating.

To test this, Wong used cow blood and cerebrospinal fluid samples, provided by his colleague Martin Groschup from the Friedrich-Loeffler-Institute, Germany, that had been collected every spring, summer and autumn over a 4 year period. ‘This allowed us to test if the cow HP complexes also oscillate in a seasonal manner analogous to chipmunk HP complexes’, explains Wong. Having used antibodies that recognised the HP complex protein to measure the protein's levels in both body fluids, Wong admits that he was impressed to see that the complex peaked in the cow's cerebrospinal fluid in February, just like in the hibernating chipmunks. The team also showed that the complex was produced by the cow's liver, was composed of three HP proteins and that each protein was modified with sugar molecules, just like in the HP complex in chipmunk blood. And when the team tested whether the HP complex could produce hibernation effects when injected into mice, they found that the rodents ate less, although they did not drop into hibernation.

‘The HP genes are not unique to hibernators’, says Wong, who adds, ‘They are conserved in non-hibernating mammals and the HP complexes likely regulate physiological functions distinct from hibernation’. Wong cautiously suggests that the complex may regulate food intake in non-hibernators, but emphasises that this result needs to be retested in an animal that possesses HP genes. And, having shown that the HP complex is not the essential switch that throws animals into hibernation, Wong says, ‘Until hibernation-specific genes are found, it is more likely that differential gene expression and/or re-wiring of existing endocrine circuits enable hibernators to hibernate’.

M. M.
M. S.
P. S.
M. H.
G. W.
Seasonal oscillation of liver-derived hibernation protein complex in the central nervous system of non-hibernating mammals
J. Exp. Biol.