A combination of cytogenetic and molecular analyses has shown that several different transposable elements are involved in the restructuring of Drosophila chromosomes. Two kinds of elements, P and hobo, are especially prone to induce chromosome rearrangements. The mechanistic details of this process are unclear, but, at least some of the time, it seems to involve ectopic recombination between elements inserted at different chromosomal sites; the available data suggest that these ectopic recombination events are much more likely to occur between elements in the same chromosome than between elements in different chromosomes. Other Drosophila transposons also appear to mediate chromosome restructuring by ectopic recombination; these include the retrotransposons BEL, roo, Doc and I and the foldback element FB. In addition, two retrotransposons, HeT-A and TART, have been found to be associated specifically with the ends of Drosophila chromosomes. Very limited data indicate that transposon-mediated chromosome restructuring is occurring in natural populations of Drosophila. This suggests that transposable elements may help to shape the structure of the Drosophila genome and implies that they may have a similar role in other organisms.

The recurring intrachromosomal rearrangements observed in an unstable X chromosome, designated Uc, of Drosophila melanogaster are shown to be mediated by hobo transposable elements. Each of 29 chromosome rearrangement breakpoints in 16 gross aberrations detected in the Uc-derived X chromosomes had a hobo element. In one particular unstable X chromosome line selected for detailed studies, a hobo element was found in each of the five hot spots for rearrangements. Furthermore, hobo elements at deletion hot spots were found to lie in the same orientation, whereas those hobo elements at inversion hot spots were in the opposite orientation. The restriction maps of two phage A clones containing rearrangement breakpoints indicated that a hobo element was inserted exactly at the breakpoints. Pairing of hobo elements in the same chromosome followed by recombination between the paired hobo elements is suggested as the explanation for the intrachromosomal aberrations observed in the Uc X chromosomes. A clear qualitative difference among the hobo elements in their ability to participate in rearrangement formation was noted. It was also found that each of the 11 recessive lethal mutations mapped in the 6F1-2 doublet had a hobo element in the doublet, whereas none of the 16 independent revertants of the mutation had a hobo element in the site. This observation indicates that hobo movement is responsible for production and subsequent instability of recessive lethal mutations in the 6F region of the Uc X chromosomes.

The cytogenetic region 46C-F on the right arm of Drosophila chromosome 2, which contains the homolog of the human jun proto-oncogene, has been genetically mapped and characterized. This project led to the identification and characterization of a Jra (jun-related antigen) mutation, which has been described in detail elsewhere. Three mutagens, EMS, DEB and gamma-rays, were used to isolate 126 lethal lines for this interval. Complementation analysis of the 126 lethal lines identified 29 lethal complementation groups in the region; nine of which have now been correlated with known genes or phenotypes. The region has been subdivided into ten intervals using various small deletions, seven intervals in 46C/D and three intervals in 46E/F. Sixteen P-element lines have been mapped to this interval and are allelic to eight of our complementation groups. The remaining unidentified complementation groups have been analyzed for critical phase, which is when the first observable defect arises and/or when death occurs. There are twelve embryonic lethal groups and seven larval lethal groups. Three lines show visible abnormalities in gut and tracheal development prior to death.

Salivary-gland chromosomes of 54 methyl methanesulphonate-and 50 triethylene melamine-induced X-chromosome recessive lethals in Drosophila melanogaster were analysed. Two of the lethals induced by the monofunctional agent and 11 of those induced by the polyfunctional agent were found to be associated with detectable aberrations. A complementation analysis was also done on 82 ethyl methanesulphonate-and 34 triethylene melamine-induced recessive lethals in the zeste-white region of the X chromosome. The EMS-induced lethals were found to represent lesions affecting only single cistrons. Each of the 14 cistrons in the region known to mutate to a lethal state was represented by mutant alleles, but in widely different frequencies. Seven of the TEM-induced lethals were associated with'deletions, only one of which had both breakpoints within the mapped region. Twenty-six of the 27 mutations in which only single cistrons were affected were mapped to 7 of the 14 known loci. One TEM-and two EMSinduced mutations were alleles representing a previously undetected locus in the zeste-white region.

Mutations arising in dysgenic hybrids of Drosophila melanogaster were collected in the zeste-white region of the X chromosome. A preponderance of the mutations affected the zwl locus; many of these were associated with structural abnormalities including inversions, deficiencies, and insertions in the 3A3-4 region of the polytene chromosome map. The extreme sensitivity of the zwl locus to the mutator activity of dysgenic hybrids contrasted with the apparent insensitivity of the zw2 locus. Other loci in the zeste-white region were weakly sensitive to the mutator activity. Insertions of two and six bands were seen between bands 3A4 and 3A6 in the chromosomes of one of the zwl mutant stocks examined. Another insertion was detected at position 2F4-5 in a different stock. Many of the mutant chromosomes were evidently unstable, as judged by secondary breakage in other parts of the X chromosome. The cytogenetic data are consistent with the idea that mutations arising in dysgenic hybrids are caused by transposable elements which insert preferentially at certain sites on the chromosomes.Hybrid dysgenesis (HD) is a condition noted in the offspring of certain Drosophila strains (1-4). Its appearance is nonreciprocal, meaning that dysgenic hybrids are produced when males of a paternally contributing (P) strain are mated with females of a maternally contributing (M) strain but usually not when the reciprocal cross is performed. Dysgenic hybrids are characterized by high sterility, male recombination, segregation distortion, enhanced mutability, and chromosome breakage.We have studied the last two phenomena by analyzing a small region of the Drosophila X chromosome in which mutations from dysgenic hybrids (HD mutations) were collected. The region selected consists of 17 genes, demarcated by the gt (giant) locus on the left and the w (white) locus on the right. It is known as the zw (zeste-white) region, having been named for two of its loci which produce conspicuous eye color mutations (5). Each of the 17 genes in this region appears to correspond to a single band in the polytene chromosomes of the salivary gland cells (refs. 5-7 Cytogenetic Analysis. Preliminary complementation tests were performed with each zw mutation shortly after it was identified. A series of tester stocks, including partial deficiencies for the zw region, were available for this purpose. The definitive complementation analysis of each zw mutation was performed later, in conjunction with the detailed cytological analysis of each zw mutant chromosome. The procedure was to mate a single zw-l/Bsw +y+ Y(or zw-visible/Y) male from each mutant line to y59bz w'ct6ffemales and also to DB/FM6, 1(1 )69aAbbreviation: HD, hybrid dysgenesis. 6042The publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U. S. C. §1734 solely to indicate this fact.