Part of the heterochronic gene
lin-42 (1) shows significant similarity to the Drosophila and vertebrate per circadian clock genes. This encompasses the PAS domain (and adjacent PAC domain) found in many clock genes. One of most interesting aspect of the Drosophila per gene is that mutations affect not only the circadian clock but also two other timing processes, temperature-dependent development and a temperature-compensated ultradian clock modulating the male's courtship song (2). The defecation oscillator of C. elegans L4 larvae is characterised by a remarkable regularity of the period under a given set of conditions while being highly dependent on temperature and nutritional status. Because of its regularity, it is possible to distinguish between effects on period length and cycle variability in mutants. For example, the period in the
clk-1 (
qm30) mutant is 50% longer whereas the regularity remains close to that of the wild type. Since defecation is a permanently recurring process, it may be difficult to decide when a mutant is 'arrhythmic'. However, we found that in a presumptive
lin-42 null mutant (
mg152 [a gift of Ann Rougvie]), regularity was completely lost, with an increase in the mean coefficient of variation for the 15 cycles of a single L4 from 3.5% to 23.1%. It seems justified to call this arrhythmicity. When we looked at a second
lin-42 allele (
n1089 [from the CGC]), we found it to be temperature-sensitive for the oscillator phenotype. At 20degC, period regularity of larvae was close to wild type. At 25degC, the strain became similar to the null mutant. The LIN-42 protein thus appears to play a crucial role in conferring to the defecation oscillator its remarkable regularity. We have recently described a circadian clock in C. elegans (3) and our preliminary investigation indicates that the two alleles behave similarly with respect to the circadian clock, i.e. arrhythmicity in the null mutant and the ts strain at 25degC but close to normal circadian rhythms in the ts strain at 20degC. Like the Drosophila per gene,
lin-42 thus appears to be involved in at least 3 different timing processes on different time scales and with different characteristics. Its role in the ultradian and circadian rhythms is now under closer investigation. (1) Jeon M et al (1999) Similarity of the C. elegans developmental timing protein LIN-42 to circadian rhythm proteins. Science 286:1141-1146. (2) Kyriacou CP & Hall JC (1994) Genetic and molecular analysis of Drosophila behavior. Adv. Genet. 31:139-186. (3) Kippert F, Saunders DS & Blaxter ML (2001) C. elegans has a circadian clock. Curr. Biol., in press Strain (30 L4 each) Temperature (degC) Period (sec) Shortest mean (sec) Longest mean (sec) Shortest cycle (sec) Longest cycle (sec) N2 20degC 49.4 46.2 53.5 44 58 N2 25degC 38.2 35.9 42.2 34 44
clk-1 (
qm30) 20degC 77.5 70.8 86.5 66 92
lin-42 (
n1089) 20degC 52.8 46.7 58.4 43 65
lin-42 (
n1089) 25degC 50.5 36.0 62.5 24 91
lin-42 (
mg152) 20degC 53.3 43.1 71.4 22 118 Strain (30 L4 each) Temperature (degC) Standard deviation Coefficient of variation (%) Mean of CVs (%) Lowest CV (%) Highest CV (%) N2 20degC 2.2 4.5 3.5 1.7 5.5 N2 25degC 1.9 5.0 3.7 2.8 5.6
clk-1 (
qm30) 20degC 5.3 6.8 4.6 2.3 6.1
lin-42 (
n1089) 20degC 3.6 6.8 4.2 2.3 7.6
lin-42 (
n1089) 25degC 6.7 13.3 14.1 7.2 27.8
lin-42 (
mg152) 20degC 7.6 14.2 23.1 10.6 46.2