Isolation and Analysis of Six timeless Alleles That Cause Short- or Long-Period Circadian Rhythms in Drosophila

Corresponding author: Michael W. Young, Rockefeller University, 1230 York Ave., New York, NY 10021., young{at}rockvax.rockefeller.edu (E-mail)

Communicating editor: J. J. LOROS

In genetic screens for Drosophila mutations affecting circadian locomotion rhythms, we have isolated six new alleles of the timeless (tim) gene. Two of these mutations cause short-period rhythms of 21–22 hr in constant darkness, and four result in long-period cycles of 26–28 hr. All alleles are semidominant. Studies of the genetic interactions of some of the tim alleles with period-altering period (per) mutations indicate that these interactions are close to multiplicative; a given allele changes the period length of the genetic background by a fixed percentage, rather than by a fixed number of hours. The tim^L1 allele was studied in molecular detail. The long behavioral period of tim^L1 is reflected in a lengthened molecular oscillation of per and tim RNA and protein levels. The lengthened period is partly caused by delayed nuclear translocation of TIM^L1 protein, shown directly by immunocytochemistry and indirectly by an analysis of the phase response curve of tim^L1 flies.

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