Cloning of mouse BMAL2 and its daily expression profile in the suprachiasmatic nucleus: a remarkable acceleration of Bmal2 sequence divergence after Bmal gene duplication.

Brain-Muscle-Arnt-Like-protein 2 (BMAL2; Arnt4) (aryl hydrocarbon receptor nuclear translocator) is a recently identified basic Helix-Loop-Helix-Per-Arnt-Sim (bHLH-PAS) transcription factor, which contributes to a positive regulation of autoregulatory feedback loop in vertebrate circadian clock systems. In this study, we cloned cDNAs encoding mouse and rat BMAL2 (mBMAL2 and rBMAL2) from mouse midbrain and rat-1 fibroblast cells, respectively. A phylogenetic analysis strongly suggested that vertebrate Bmal1 and Bmal2 genes were generated by a single gene duplication of an ancestral Bmal gene, a vertebrate ortholog of dCyc gene, and that 'BMAL2's putatively termed so far are orthologous. Interestingly, BMAL2 proteins have diverged about 20-fold more rapidly than BMAL1 proteins after the duplication, suggesting an as-yet-unidentified function conserved in BMAL1 but not in BMAL2. mBmal2 mRNA was constitutively expressed throughout the day under light-dark cycle in the mouse hypothalamus containing suprachiasmatic nucleus, the site of the central circadian oscillator in mammals.