We have used a strain of genotype
dpy-8 -2 een for animals homozygous for autosomal recessive mutations that lead to defects in recombination.
dpy-8 and
lon-2 are closely linked (0.6 map unit), as are
unc-3 and
unc-7 (1.7 map units); but the
dpy-8 to
unc-3 distance is 25 map units. Over 98% of the wild-type self progeny of this strain are heterozygous for all four loci because the two members of each closely linked pair tend to balance each other. About 11% of the wild-type progeny are
dpy-8 -2 of the original genotype, owing to recombination in the large interval separating the pairs of loci, but this matters very little, because either quadruple heterozygote generates the following four easily distinguished recombinant types, each at a frequency of about 10%: Dpy non-Unc, Lon non-Unc, Unc-3 non-Dpy non-Lon, Unc-7 non-Dpy non-Lon. Our screen thus involves mutagenizing with EMS and picking first and second generation wild-type progeny. The broods of F2 animals are then screened for the absence of recombinant types, which usually comprise 40% of the progeny. This method largely excludes from consideration X linked recessive mutations, because we are selecting for continued heterozygosity of the X chromosomes. We have so far screened the broods of about 4,400 fertile F2 animals and found one mutant, which has been outcrossed three times. Its recombination frequency for the
dpy-8 to
unc-3 interval on the X chromosome is about 0.3% (1/80 the wild-type value), it gives about 33% male self-progeny, and it shows noncomplementation with
him-8(
e1489) IV. We note that among the recessive him mutants described by Hodgkin, Horvitz and Brenner (1979, Genetics 91:67),
him-8(
e1489) showed the most drastic effects on X-chromosome recombination (giving about 1/8 the wild-type value in the
lon-2 to
unc-7 interval); autosomal recombination was not reduced. Paul Goldstein (1982, Chromosoma 86:577) has shown that
him-8(
e1489) hermaphrodites have six synaptonemal complexes, indicating that the mutant gene does not seem to affect chromosome pairing. Because genetic exchange precedes disjunction, we suggest that the primary defect in
him-8 mutants is in X-chromosome recombination, and that reduced exchange leads to enhanced X-chromosome nondisjunction. In many species, exchange between homologues is essential to orderly chromosome segregation at meiosis. We suggest that this rule also applies to C. elegans. If so, mutant hermaphrodites in which recombination of all chromosomes is drastically reduced might be expected to produce almost exclusively inviable zygotes, owing to aneuploid chromosome compositions. This could explain why we have so far not recovered any such mutant.