COMPARISON OF CHROMOSOMAL DNA COMPOSING TIMELESS IN DROSOPHILA-MELANOGASTER AND DROSOPHILA-VIRILIS SUGGESTS A NEW CONSERVED STRUCTURE FOR THE TIMELESS PROTEIN

Two proteins, TIM and PER, physically interact to control circadian cy cles of tim and per transcription in Drosophila melanogaster. In the p resent study the structure of TIM protein expressed by D.virilis was d etermined by isolation and sequence analysis of genomic DNA (gDNA) cor responding to the D.virilis tim locus (vtim). Comparison of vtim and m tim gDNA revealed high conservation of the TIM protein. This contrasts with poor sequence conservation previously observed for the TIM partn er protein PER in these species. Inspection of the vtim sequence sugge sts an alternative structure for most TIM proteins. Sequences forming an intron in a previously characterized D.melanogaster tim cDNA appear to be most often translated to produce a longer TIM protein in both s pecies. The N-terminal sequence of vTIM and sequence analysis of genom ic DNA from several strains of D.melanogaster suggest that only one of two possible translation initiation sites found in tim mRNA is suffic ient to generate circadian rhythms in D.melanogaster. TIM translation may be affected by multiple AUG codons that appear to have been conser ved in sequences composing the 5'-untranslated tim mRNA leader.