Biological clock in total darkness: The Clock / MOP3 circadian system of the blind subterranean mole rat

doi:10.1073/pnas.181484498

Biological clock in total darkness: The Clock/MOP3 circadian system of the blind subterranean mole rat

^*Institute of Evolution, University of Haifa, Mount Carmel, Haifa 31905, Israel; and ^†Max Planck Institute for Experimental Endocrinology, 30625 Hannover, Germany

Contributed by Eviatar Nevo

Abstract

Blind subterranean mole rats retain a degenerated, subcutaneous, visually blind but functionally circadian eye involved in photoperiodic perception. Here we describe the cloning, sequence, and expression of the circadian Clock and MOP3 cDNAs of the Spalax ehrenbergi superspecies in Israel. Both genes are relatively conserved, although characterized by a significant number of amino acid substitutions. The glutamine-rich area of Clock, which is assumed to function in circadian rhythmicity, is expanded in Spalax compared with that of humans and mice, and is different in amino acid composition from that of rats. We also show that MOP3 is a bona fide partner of Spalax Clock and that the Spalax Clock/MOP3 dimer is less potent than its human counterpart in driving transcription. We suggest that this reduction in transcriptional activity may be attributed to the Spalax Clock glutamine-rich domain, which is unique in its amino acid composition compared with other studied mammalian species. Understanding Clock/MOP3 function could highlight circadian mechanisms in blind mammals and their unique pattern as a result of adapting to life underground.

Footnotes

↵ ‡ To whom reprint requests should be addressed. E-mail: nevo{at}research.haifa.ac.il.
Data deposition: The sequences reported in this paper have been deposited in the GenBank database (accession nos. AJ318057–AJ318060).
↵ § Kushnirov, D., Beolchini, F., Lombardini, F. & Nevo, E. (1998) Euro-American Mammal Congress, July 19–24, 1998, Santiago de Compostela, Spain, abstr. 381.
Abbreviations:

RT,

reverse transcriptase;

bHLH,

basic helix–loop–helix;

SCN,

suprachiasmatic nucleus;

RLU,

relative light unit;

polyQ,

polyglutamine;

hClock,

human Clock;

sClock,

Spalax Clock