Worm Breeder's Gazette 12(4): 56 (October 1, 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.

A Cis-Acting Locus that Promotes Recombination Between the X Homologs

Anne M. Villeneuve

Department of Developmental Biology, Stanford University School of Medicine, Stanford, CA 94305

Among the mutations identified in my screens for mutants with increased non-disjunction, I have identified one mutation, me8 ,that defines a cis-acting locus important for promoting normal levels of reciprocal recombination between the two X homologs, thereby ensuring their proper disjunction. The me8 mutation specifically affects segregation of the X chromosome, and maps near or to the left of egl-17 ,the leftmost known genetic marker on the X chromosome. Based on previous studies examining the genetic behavior of reciprocal translocations and X chromosome Dps, it had already been proposed that this general region of the X chromosome contains one or more sites involved in normal pairing and segregation of the X homologs (1, 2, 3).

The me8 mutation is semi-dominant: me8 / me8 hermaphrodites produce 10% self-progeny males, while me8 /+hermaphrodites produce 1.5% males. This semi-dominance is due to a loss of function, since hermaphrodites heterozygous for chromosomal deletions of the locus ( meDf2 -61+)also show an increase in the level of X nondisjunction, producing 8%a males. The fact that me8 /+is less mutant than Dp+ suggests that the me8 mutation only partially disrupts the locus, or that there are other similar loci in the deleted region. Increased non-disjunction is not a general property of X chromosome Dfs; Dfs of other regions of X have no effect on X disjunction.

me8 /Dfor Dp; DpDf hermaphrodites show a dramatically high level of X nondisjunction, producing broods composed of >35% males and 6-7% XXX animals. This high non-disjunction in me8 /Dfand Df/Df is correlated with an 85-90% decrease in recombination between the X homologs, as evidenced both by reductions in genetic map distances and by the presence of univalent (non-crossover) X chromosomes in cytological preparations of oocyte nuclei. Chromosomal duplications of the wild-type region that are unlinked to the X chromosome cannot complement this high rate of non-disjunction in trans, indicating that the locus must act in cis to promote recombination between the X homologs and thereby ensure their disjunction.

The data suggest a model in which the me8 cis-acting locus acts as a "pairing site" involved in nucleating or facilitating the assembly of a recombination-competent complex between the X homologs; this may take place after, or may be required for, a DNA homology search that allows the identification of appropriate pairing partners. The locus might act as a binding site that recruits trans-acting factors onto the chromosomes, initiating assembly of a complex which proceeds in a polar fashion along the length of the homologs. A variation on this model is that the locus serves as a "molecular address", targeting the chromosome to a specific location in the nucleus, presumably the nuclear envelope; this localization then serves to facilitate complex assembly. This type of model is appealing since the me8 locus maps to the very end of the X chromosome, and chromosome ends are known to be associated with the nuclear envelope during mid-prophase of meiosis (pachytene) in a variety of systems, including C. elegans (4).

It was initially a surprise to find that heterozygosity for a deletion of the entire region ( meDf6 )implicated in the X;A translocation studies has only a modest effect on X chromosome disjunction, since reciprocal translocations (and Df-translocations isolated in this study) with similar breakpoints cause high non-disjunction and strong crossover suppression. I propose that two factors contribute to the aberrant recombination and segregation behavior observed in translocation heterozygotes: 1) the majority of X has been separated from the cis-acting locus defined by me8 and the Dfs, and 2) the chromosome has been sequestered to a new location or in a configuration that makes it unavailable to assemble into a recombination-competent complex with its homolog.

a Numbers are corrected to account for inviabilily of Df hemizygotes and homozygotes.

Literature Cited:

1. Herman, R. K., Kari, C. K, and Hartman, P. S. Genetics 102, 379-400 (1982).

2. McKim, K. S., Howell, A. M. and Rose, A. M. Genetics 120, 987-1001 (1988).

3. Herman, R. K. and Kari, C. K. Genetics 121, 723-737 (1989).

4. Goldstein, P., and Slaton, D. E. Chromosoma 84, 585-97 (1982)