We demonstrated that a subterranean, visually blind mammal has a functional set of three Per genes that are important components of the circadian clockwork in mammals. The mole rat superspecies Spalax ehrenbergi is a blind subterranean animal that lives its entire life underground in darkness. It has degenerated eyes, but the retina and highly hypertrophic harderian gland are involved in photoperiodic perception. All three Per genes oscillate with a periodicity of 24 h in the suprachiasmatic nuclei, eye, and harderian gland and are expressed in peripheral organs. This oscillation is maintained under constant conditions. The light inducibility of sPer1 and sPer2, which are similar in structure to those of other mammals, indicates the role of these genes in clock resetting. However, sPer3 is unique in mammals and has two truncated isoforms, and its expressional analysis leaves its function unresolved. Per's expression analysis in the harderian gland suggests an important participation of this organ in the stabilization and resetting mechanism of the central pacemaker in the suprachiasmatic nuclei and in unique adaptation to life underground. L ife on Earth is adapted to cyclical phenomena imposed by the external environment (1). Most organisms have circadian systems that synchronize physiological events to the external 24-h cycle (2). The underlying molecular-genetic mechanisms of these clocks exhibit an extraordinary evolutionary conservation from cyanobacteria through plants, fruit flies, and mammals. All of these clock systems consist of autoregulatory transcriptional͞ translational feedback loops with positive͞negative regulatory elements and similar genetic machinery (3, 4).Two basic helix-loop-helix PAS (PER-ARNT-SIM) transcription factors, CLOCK and MOP3 (BMAL1), form the positive elements of the system and drive transcription of three Period (Per 1, 2, 3) and two Cryptochrome (Cry 1, 2) genes. The protein products of these genes are thought to be components of a negative feedback complex that inhibits the CLOCK͞MOP3 heterodimer, thereby closing the circadian loop.The enigma of circadian rhythms in a blind subterranean mammal is intriguing (5-7). We have already shown that a CLOCK͞MOP3-driven clock exists in Spalax (8). Here we continue to decipher its circadian machinery.
The Evolutionary Model of Blind Subterranean MammalsThe blind subterranean mammals, mole rats of the Spalax ehrenbergi superspecies in Israel, consist of four species that have been studied multidisciplinarily as an evolutionary model of speciation and adaptation (5-7). Spalax lives in total darkness, yet, it perceives the daily and seasonal temporal cycles underground (9). Behaviorally, Spalax displays polyphasic and polytypic day-night activity patterns (10, 11) coupled with polymorphic (12) and seasonal ʈ variation, supported by a unique photoperiodic perception mechanism (9). Spalax has a degenerated s.c. functional eye (13,14), which, together with the harderian gland, participates in photoperiodic perception (9, 15-18). The retina h...