An unusual coding sequence from a Drosophila clock gene is conserved in vertebrates

The per locus has a fundamental involvement in the expression of biological rhythms in Drosophila. Mutations at this locus can shorten, lengthen or eliminate a variety of rhythmic activities that range from circadian behaviours, exemplified by eclosion and locomotor activities^1,2, to short-period behaviour such as the 55-s rhythm of courtship song³. DNA from the per locus has been cloned^4-7, and we have used P-element-mediated DNA transformation to establish that a 7.1-kilobase (kb) HindIII fragment contains a functional copy of the gene. This transforming DNA contains a single transcription unit which gives rise to a 4.5-kb poly(A)⁺ RNA⁵. Here we report the results of a search for sequences homologous to the per locus DNA in the genomic DNA of several species of vertebrates. An unusual, tandemly repeated sequence forming a portion of the 4.5-kb per transcript is homologous to DNA in chicken, mouse and man. Cloned DNAs from the mouse and Drosophila are related by long, uninterrupted tandem repetitions of the sequence ACNGGN. At the per locus, these tandem repeats are predicted to code for poly(Thr-Gly) tracts up to 48 amino acids long. These repeated sequences are also transcribed in the mouse. Several long tracts of poIy(Thr-Gly) appear to be encoded by DNA cloned from the mouse.