Worm Breeder's Gazette 12(2): 46 (January 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.

Dosage Compensation and a Very Small Protein

David Hsu, Barbara Meyer

Figure 1

Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720

dpy( y130 )is required for the hermaphrodite mode of X-chromosome dosage compensation. Homozygous y130 animals display a maternal-effect, XX-specific lethality characteristic of dosage compensation upsets. This lethality is temperature sensitive. dpy( y130 )differs from the other dosage compensation dpy genes in several respects. Unlike the other dpy genes involved in the control of dosage compensation, the dpy( y130 )maternal-effect lethality is completely penetrant at the restrictive temperature. In addition, dpy( y130 )appears to function in XO animals. y130 XO animals are viable, however, they are scrawny, slow growing and mating defective.

In order to better understand how dosage compensation functions at a molecular level, we cloned dpy( y130 ).Groups of cosmids near myo-3 (0.1 map units away from y130 ),were assayed for their ability to rescue the maternal-effect lethality in germline transformation assays. Rescuing activity was localized to cosmid C09F3 .Subsequent rescue experiments narrowed the rescuing region to a 1.2 kb region of this cosmid. Northern blot analysis using this region as a probe detects a highly abundant 0.7kb transcript expressed throughout all stages of development.

Using the minimal rescuing fragment as a probe, we isolated cDNA's corresponding to this transcript (Libraries from Stuart Kim and Serge Lichtsteiner). Sequence analysis of these cDNA's and the corresponding genomic region identifies a 372 nucleotide open reading frame encoding a 13kd protein (Figure 1). This protein appears to have no significant homology to anything in the protein databases. To confirm that this small ORF was indeed coding for the dpy( y130 )protein, frameshift mutations were introduced in the coding region. These frameshift mutations were not able to rescue the y130 maternal-effect lethality.

Sequence analysis of the y130 mutation reveals a Gly to Arg change in the protein. Much to our dismay, sequencing of new alleles obtained in a non-complementation screen ( y185 , y186 )revealed that they result in the same nucleotide change. Thus the null phenotype of dpy( y130 )remains unclear. Current efforts are being directed at the isolation of new alleles in order to better define the null phenotype.

[See Figure 1]

Figure 1