Worm Breeder's Gazette 14(5): 29 (February 1, 1997)

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.

Mutation via Gene Conversion

Jonathan Zalevsky, Anne Villeneuve

Department of Developmental Biology, Stanford University School of Medicine, Stanford, CA 94305-5427

        We previously reported that the him-14 gene, which is required
for the formation of meiotic crossovers, corresponds to ZK1127.11, a
gene encoding a member of the MutS family of mismatch repair proteins. 
The genome sequencing consortium has also identified a partial
duplication (termed T02G5.6) of this gene on the adjacent cosmid. 
Specifically, a 1.1 kb segment of genomic DNA including both exons and
introns is duplicated at a position 10 kb from the intact him-14 gene;
this DNA segment shares >96% sequence identity with the him-14 gene  The
duplicated segment duplicates nearly 30% of the him-14  coding region,
but it is not expected to produce any functional protein since it not
only lacks both the 5' and 3' ends, but also includes a base
substitution and a base deletion that produce in frame stop codons.  
        The presence of this gene duplication is not remarkable in and
of itself, since partial gene duplications of this type are reasonably
common in the C. elegans genome, as was noted in the 1994 Nature article
reporting on the first 2.2 Mb of sequence.  Despite their frequent
occurrence in the worm genome, the origins and consequences of these
duplications remain unknown.
        We report here that a duplicated gene segment can serve as a
donor of genetic information in a gene conversion event involving the
intact gene as the recipient.  In the course of sequencing him-14
alleles, we found that the mutant allele it21  (isolated following EMS
mutagenesis) contains numerous base changes over a 350 bp region, and
that these changes all correspond to the sequence present at the T02G5.6
locus.  We know that this was a gene conversion event rather than a gene
fusion since the template for sequencing was a PCR product amplified
using primers from the him-14 gene that flank the duplicated portion;
other data confirm that the downstream region of the him-14 gene is
intact in the it21 mutant.  The changes incorporated result in several
amino acid substitutions as well as truncation of the protein upstream
of a conserved putative helix-turn-helix thought to be involved in
important protein/protein interactions.
        We wonder how common this type of gene conversion event might
be, and are interested in hearing from anyone else who has observed
similar mutational events.