There are numerous examples of the regular segregation of achiasmate chromosomes at meiosis I in Drosophila melanogaster females. Classically, the choice of achiasmate segregational partners has been thought to be independent of homology, but rather made on the basis of availability or similarities in size and shape. To the contrary, we show here that heterochromatic homology plays a primary role in ensuring the proper segregation of achiasmate homologs. We observe that the heterochromatin of chromosome 4 functions as, or contains, a meiotic pairing site. We show that free duplications carrying the 4th chromosome pericentric heterochromatin induce high frequencies of 4th chromosome nondisjunction regardless of their size. Moreover, a duplication from which some of the 4th chromosome heterochromatin has been removed is unable to induce 4th chromosome nondisjunction. Similarly, in the absence of either euchromatic homology or a size similarity, duplications bearing the X chromosome heterochromatin also disrupt the segregation of two achiasmate X chromosome centromeres. Although heterochromatic regions are sufficient to conjoin nonexchange homologues, we confirm that the segregation of heterologous chromosomes is determined by size, shape, and availability. The meiotic mutation Axs differentiates between these two processes of achiasmate centromere coorientation by disrupting only the homology-dependent mechanism. Thus there are two different mechanisms by which achiasmate segregational partners are chosen. We propose that the absence of diplotene-diakinesis during female meiosis allows heterochromatic pairings to persist until prometaphase and thus to co-orient homologous centromeres. We also propose that heterologous disjunctions result from a separate and homology-independent process that likely occurs during prometaphase. The latter process, which may not require the physical association of segregational partners, is similar to those observed in many insects, in Saccharomyces cerevisiae and in C. elegans males. We also suggest that the physical basis of this process may reflect known properties of the Drosophila meiotic spindle.

The decapentaplegic (dpp) locus of Drosophila melanogaster is a >55 kb genetic unit required for proper pattern formation during the embryonic and imaginal development of the organism. We have proposed that these morphogenetic functions result from the action of a secreted transforming growth factor-13 (TGF-13)-related protein product encoded by dpp. In this paper we localize 60 mutations on the molecular map of dpp. The positions of these mutations cluster according to phenotypic class, identifying the locations of specific dpp functions. By Northern and cDNA analysis, we characterize five overlapping dpp transcripts. On the basis of the locations of the overlaps relative to a previously sequenced cDNA, it is likely that these transcripts all encode similar or identical polypeptides. We propose that the bulk of dpp DNA consists of extensive arrays of cisregulatory information. The large (>25-kb) 3' c/s-regulatory region represents a novel feature of dpp gene organization.

Meiotic pairing has now been shown to require heterochromatic homology and to be sensitive to repeat number in both male and female Drosophila. The increased pairing ability of repetitive sequences could be one reason that most eukaryotes allow the accumulation of tandem repeated elements. This may well be a reflection of a general role for heterochromatin, and at least a partial explanation of the ubiquity of heterochromatin through the eukaryotes.

The mouse B-cell lymphoma WEHI 279.1 is a tumor which synthesizes both membrane and secreted immunoglobulin M (IgM). We have immunoselected variants which fail to express the membrane form (mIgM-); the most frequently isolated phenotype is a complete loss of both membrane expression and synthesis of the mu heavy chain within the cells. We have chosen four of these mIgM- mutants for detailed molecular investigation. One of these has suffered a large deletion which covers the region of chromosome 12 containing the expressed mu gene, but three have no detectable changes in the DNA arrangement of the mu gene. All of the mutants, including the deletion mutant, synthesize 10-30% of the wild-type level of cytoplasmic mu RNA; however, none is the appropriate size for membrane mu (mu m) or secreted mu (mu s) message. Based on our studies of the deletion mutant, which retains its nonproductively arranged allele, at least some of these RNAs may be 'sterile' transcripts from the nonproductively arranged allele. However, if all of these mRNAs derive from the other allele, they represent a substantial elevation of these sterile messages relative to the wild-type level. Furthermore, the three nondeletion mutants transcribe mu RNA at a level indistinguishable from the wild type. It is likely that their defects lie in the stability, processing, or transport of the mu RNA within the nucleus. Somatic cell hybrids between P3X and the IgM- variants produced mostly mIgM- hybrids. However, a few mIgM+ hybrids were produced, suggesting that the mu- defects may be partly complemented by the P3X fusion partner.

The regular segregation of achiasmate chromosomes in Drosophila melanogaster females is ensured by two distinct segregational systems. The segregation of achiasmate homologs is assured by the maintenance of heterochromatic pairing; while the segregation of heterologous chromosomes is ensured by a separate mechanism that may not require physical association. AxsD (Aberrant X segregation) is a dominant mutation that specifically impairs the segregation of achiasmate homologs; heterologous achiasmate segregations are not affected. As a result, achiasmate homologs frequently participate in heterologous segregations at meiosis I. We report the isolation of two intragenic revertants of the AxsD mutation (Axsr2 and Axsr3) that exhibit a recessive meiotic phenotype identical to that observed in AxsD/AxsD females. A third revertant (Axsr1) exhibits no meiotic phenotype as a homozygote, but a meiotic defect is observed in Axsr1/Axsr2 females. Therefore mutations at the AxsD locus define a gene necessary and specific for homologous achiasmate segregation during meiosis. We also characterize the interactions of mutations at the Axs locus with two other meiotic mutations (ald and ncd). Finally, we propose a model in which Axs+ is required for the normal separation of paired achiasmate homologs. In the absence of Axs+ function, the homologs are often unable to separate from each other and behave as a single segregational unit that is free to segregate from heterologous chromosomes.