Worm Breeder's Gazette 10(2): 53

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An Allelic Series of mei-1(I)

Paul Mains, Ingrid Sulston and W.B. Wood

Figure 1

We have previously described the interactions between alleles of mei-
1(I) and the mutations ct46(I) and ct61(I) [Mains et al., WBG 10(1)
:102].  The latter two mutations produce gain-of-function 'poison' 
gene products that result in dominant, temperature-sensitive maternal-
effect lethality.  The mutations are linked, but represent different 
loci separated by 2 cM.  Mutations of mei-1 show nonconditional 
recessive maternal-effect lethality resulting from a failure of 
meiosis; the canonical allele (b284) was isolated in a screen for 
maternal-effect lethals [Sprunger and Kemphues, WBG 10(1):100].  This 
mutation is an efficient trans-dominant suppressor of both ct46 and 
ct61.  Previously, we had isolated twelve additional alleles of mei-1 
as suppressors of ct46.  Here we show that ct46 is an allele of mei-1.
One of these suppressor mutations, ct99, was isolated in cis to ct46.  
The eggs from ct46ct99/+ + mothers show wild-type levels of hatching 
compared to l% for the eggs of ct46/+ mothers.  ct46ct99 shows 
recessive nonconditional maternal effect lethality and fails to 
complement mei-1(b284).  ct46ct99/ct46+ shows no trans-suppression of 
ct46.  An additional suppressor mutation, isolated as ct46ct101, shows 
identical behavior.  Therefore, ct101 and ct99 are cis-dominant 
suppressors of ct46 apparently resulting from intragenic loss-of-
function reversion of the ct46 gain-of-function poison product.  Thus, 
ct46 is an allele of mei-1.  Consistent with this interpretation, 
mutations in mei-1 map <0.01 cM from ct46.  These revertants occurred 
at a high frequency: 2/5500 after EMS mutagenesis, again implying that 
they are loss-of-function mutations.
While the above interpretation of the cis-dominant suppression of 
ct46 by ct99 and ct101 is straightforward, the majority of mei-1 
alleles, for example ct82, shows the surprising property of also being 
trans-dominant.  As reported previously [Mains et al., op.  cit.], 92% 
of the eggs from ct46ct82/ct46+ mothers hatch.  Twelve alleles of mei-
1 (defined by the failure to complement for the recessive maternal 
effect lethality) show this property, and the trans-suppression ranges 
from 28-92%.  Like ct99 and ct101, these alleles appear to represent 
general loss-of-function rather than specific gain-of-function 
mutations that compensate for the ct46 lesion.  They were isolated at 
a very high frequency after EMS mutagenesis (11/5500); moreover, the 
canonical allele b284, which was isolated in the absence of ct46 (see 
above), is also an efficient trans-suppressor (77% of the eggs from 
ct46+/+b284 hatch).  Unlike ct99 and ct101, these mutations are also 
trans-dominant suppressors of ct61.
How can we reconcile these two classes of apparent loss-of-function 
alleles of mei-1, one which suppresses ct46 only in cis and the other 
which can suppress ct46 (and ct61) in cis or trans?  It seems likely 
that the cis-only suppressors (ct99 and ct101) are true null mutations 
(e.g., causing absence of all gene-product functions) while the trans 
suppression (ct82, b284, etc.) is mediated by the presence of a 
partially defective gene product.  Deficiencies for the region (nDf23 
and nDf24) show no trans-suppression, consistent with the 
interpretation that the cis only suppressors represent the null 
phenotype (although this interpretation is complicated by the fact 
that the deficiencies tested remove the ct61 locus in addition to mei-
1).  One possibility consistent with the evidence would be that a 
partially defective mei-1 product can form a complex with the poison 
ct46 (or ct61) gene product and thereby inactivate it, whereas a 
completely defective (or missing) mei-1 product resulting from a null 
mutation cannot.  It should be noted that Kusch and Edgar [Genetics 
113: 621 (1986)] saw a similar pattern of interactions for several 
genes affecting the cuticle (i.e.  loss-of-function mutations, but not 
true nulls, could suppress dominant gain-of-function mutations).
We may have also identified yet another class of mei-1 alleles.  The 
mutation ct103(I) is a trans-dominant suppressor of both ct46 and ct61,
but unlike the previously described mei-1 alleles shows no recessive 
maternal-effect lethality.  It complements other mei-1 alleles.  
However, it maps between lin-10 and lin-28(I), the closest markers 
that flank mei-1.Therefore, we have an allelic series of mei-1: (1) 
ct46, a dominant gain-of-function poison, (2) ct99 and ct101, putative 
null alleles that are cis-dominant suppressors of ct46 and recessive 
maternal-effect lethals, (3) ct82, b284 (and 9 others), trans-dominant 
suppressors of ct46 and ct61 and recessive maternal effect lethals, 
and (4) possibly ct103, a trans-dominant suppressor of ct46 and ct61 
with no recessive phenotype.
We have identified a mutation at another locus, ct102(I), which is 
also a trans-dominant suppressor of both ct46 and ct61.  It shows 
recessive maternal-effect lethality with defects that closely resemble 
those of mei-1 mutants (Sprunger and Kemphues, op.  cit.).  However, 
ct102 complements recessive alleles of mei-1 and maps to a different 
interval, between bli-4 and unc-37.  This locus will likely be 
designated 'mei-2'.  Finally, a second mutation that maps to this same 
interval, ct98, is also a trans-dominant suppressor of ct46 and ct61, 
but complements ct102 and shows no recessive maternal-effect lethality.
Therefore, this could be a viable allele of 'mei-2'.[See Figure 

Figure 1