Dauer-constitutive (Daf-c) mutations in the genes
daf-2 and
daf-23 extend life span (Age) (Kenyon et al., Nature 366: 461-464, Larsen et al., Genetics 139: 1567-1583). The Age phenotypes of
daf-2 and
age-1 are suppressible by a
daf-16 mutation (C. Kenyon, pers. comm., Larsen et al., Genetics 139: 1567-1583). These results suggested similar underlying defects in the
age-1 and these Daf-c mutants, and prompted us to look at the effect of
age-1 on dauer formation. Because several mutants have been identified recently that show a Daf-c phenotype at 27 but not at the standard assay condition of 25 (M. Ailion and J. H. T., pers. comm.),
age-1 strains were tested at both 25 and 27. At 27, TJ1052
age-1(
hx546) formed 100% dauers. (This phenotype is sensitive to very small fluctuations in the temperature. Differences as small as 0.5 may cause significant changes in the frequency of dauer formation.) Two other
age-1 strains (TJ412 and TJ401) also formed many dauers at 27. At 25, none of these strains formed any dauers. To confirm that the Daf-c phenotype was caused by a mutation in
age-1, the phenotype was mapped.
age-1 has been assigned to linkage group II based on its Age phenotype (Friedman and Johnson, Genetics 118:75-86). Using three-factor crosses, the Daf-c phenotype was mapped between
bli-1 and
rol-1 on chromosome II. Because the position of the Daf-c mutation was consistent with it being a
daf-23 allele, we carried out a complementation test.
daf-23(
mg44)/age-1
(hx546) heterozygotes formed 100% dauers at 27, indicating non-complementation. Both mutations are recessive. We also tested two additional
daf-23 alleles (provided by A. Koweek and G. Ruvkun), and both failed to complement
age-1. Epistasis analysis was done with
age-1 and several Daf-d mutations, and the results were similar to those found with
daf-23 and
daf-2.
daf-3,
daf-5 and
osm-5 failed to suppress
age-1, whereas
daf-16 partially suppressed
age-1. Recent results from Tom Johnson's lab indicate that several independently isolated
age-1 alleles are also dauer-constitutive (S. Duhon and T. Johnson, this issue). We conclude that
age-1 and
daf-23 are allelic and that mutations in this gene result in both Daf-c and Age phenotypes. The gene should be referred to as
age-1 in accordance with the standard nomenclature. We thank C. Kenyon, S. Duhon and T. Johnson for communicating unpublished results, and A. Koweek, H. Tissenbaum and G. Ruvkun for sending unpublished mutations.