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

Neurosci Lett. 2001 Mar 9;300(2):111-4. doi: 10.1016/s0304-3940(01)01581-6.


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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • ARNTL Transcription Factors
  • Animals
  • Basic Helix-Loop-Helix Transcription Factors
  • Biological Clocks / genetics*
  • Circadian Rhythm / genetics*
  • Cloning, Molecular
  • DNA, Complementary / genetics
  • DNA, Complementary / isolation & purification
  • Evolution, Molecular*
  • Fibroblasts / metabolism
  • Gene Duplication*
  • Gene Expression Regulation / physiology*
  • Mesencephalon / metabolism
  • Mice
  • Molecular Sequence Data
  • Neurons / metabolism
  • Phylogeny
  • RNA, Messenger / metabolism
  • Rats
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sequence Homology, Amino Acid
  • Suprachiasmatic Nucleus / cytology
  • Suprachiasmatic Nucleus / metabolism*
  • Transcription Factors / chemistry
  • Transcription Factors / genetics
  • Transcription Factors / isolation & purification*
  • Transcription Factors / metabolism


  • ARNTL Transcription Factors
  • Arntl protein, mouse
  • Arntl2 protein, mouse
  • Arntl2 protein, rat
  • Basic Helix-Loop-Helix Transcription Factors
  • DNA, Complementary
  • RNA, Messenger
  • Transcription Factors