Worm Breeder's Gazette 12(3): 104 (June 15, 1992)
These abstracts should not be cited in bibliographies. Material contained herein should be treated as personal communication and should be cited as such only with the consent of the author.
The maternal-effect gene mei-1 produces a product essential for meiosis. However, mei-1 alleles fall into no fewer than 4 distinct classes and a number of models can accommodate their genetic interactions.
The dominant mutation mei-1 ( ct46 )causes a defect in mitotic spindle formation in the l-cell embryo. Previous genetic screens for ct46 suppressors had primarily identified intragenic mutations lacking functional mei-1 activity which fell into two classes. While one of these classes contained alleles with properties consistent with null alleles, the second class contained alleles producing defective mei-1 product and were able to suppress ct46 both in cis and in trans. To extend this analysis, we designed a screen which we expected would be biased toward the isolation of extragenic suppressors. However, while 3/14 suppressors identified are apparently unlinked to mei-1 ,the remaining 11 mutations were defined as a fourth class of mei-1 alleles. In an effort to assess the relationship between this group of suppressors and the previously known mei-1 alleles, we undertook a detailed analysis of a series of intragenic trans-heterozygotes.
Our evidence suggests that dominant mei-1 mutations may stabilize a multimeric complex containing mei-1 protein resulting in the persistence of mei-1 product into mitosis and allowing misincorporation of mei-1 activity into the mitotic spindle. Alleles of mei-1 which result in the presence of a non-functional product are capable of acting as trans-suppressors of the dominant mutation by acting in a weakly antimorphic (dominant negative) manner. That is, complexes which incorporate any non-functional product are rendered inactive but not before they function in meiosis. Taken together, the genetic evidence suggests that mei-1 gene activity may exhibit a sharp temporal threshold; a relatively high level of activity is required for meiosis but must be eliminated prior to mitosis.
All three extragenic suppressors lack an apparent phenotype (other than dominant trans-suppression). Logically enough, therefore, 'we' have named the gene(s) defined by these alleles suppressors of mitotic lethality, creating an acronym that wins little favour from my supervisor. Two of these mutations map between dpy-17 and unc-93 on LG III, suggesting allelism; the third mutation has not yet been mapped. Interestingly, all three mutations are capable of dominantly transsuppressing both mei-1 ( ct46 )(as expected) and a dominant mutation at a second locus, mei-26 ( ct61 ),even though they were only selected to suppress ct46 .
The biological implications of these genetic interactions are quite interesting. Meiotic and mitotic spindles are clearly morphologically (and presumably structurally) distinct yet must perform somewhat analogous functions. One might imagine that there are a relatively large number of functionally non-interchangeable but analogous structures involved in the two processes. If this is the case, it serves to emphasize the importance of proper inactivation of meiotic structures after meiosis during worm embryogenesis. Extragenic suppressors of mei-1 dominant alleles could identify components of this 'disassembly' system.