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Genetic Analysis of the Heterochromatin of Chromosome 3

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Genetic Analysis of the Heterochromatin of Chromosome 3 Copyright 0 1988 by the Genetics Society of America Genetic Analysisof the Heterochromatin of Chromosome 3 in Drosophila melanogaster. I. Products of Compound-Autosome Detachment Gary E. Marchant and David G. Holm Department of Zoology, The Universityof British Columbia, Vancouver, British Columbia, Canada V6T 2A9 Manuscript received September 15, 1987 Revised copy accepted July 1, 1988 ABSTRACT The heterochromatin of the third chromosome is the largest uncharacterized region of the Drosophila melanogaster genome, and the last major block of D. melanogaster heterochromatin to be thoroughly analyzed. In the present study, this region was genetically dissected by generating and analyzing a series of attached, detached and reattached third chromosomes. Separate detachment experiments were conducted for all 12 possible combinations of four newly synthesized sister-strand compound-31 and three newly synthesized sister-strand compound-3R chromosomes.A total of 443 recessive lethal detachment products carrying putative heterochromatic deficiencies were tested for complementation in a several-stage complementation analysis. The results revealed the presence of seven separable vital regions in the heterochromatin of chromosome 3. Attempts to reattach defi- ciency-carrying detachment products established that six of these vital regions are on the left arm, but only one is on the right arm. An analysis of the types and frequencies of detachment-product deficiencies generated in each detachment experiment permitted the genetic characterization of the progenitor compounds. It was also possible to determine the proximal-distal orientation of the genes on each arm, and to identify possiblebreakpoints for each lethal detachment product produced. The results of this study suggestthat vital genes in the heterochromatin of the third chromosome are not randomly distributed between, nor within, the heterochromatic blocks of the left and right arms. HROMOSOME 3 of Drosophila melanogastercon- that the constitutive heterochromatin of D. melano- C tains the last major uncharted block of hetero- gaster and other organisms is almostentirely com- chromatin to be genetically analyzed in this species. posed of long, homogeneousblocks of individual sat- Heterochromatin is of two types, facultative and con- ellite DNA sequences tandemly arranged in a chro- stitutive(BROWN 1966), but only constitutive is mosome-specific order. The estimatedamount of present in the chromosomes of Drosophila. Unlike the satellite DNA in eachblock of heterochromatin almost euchromatic regionsof the genome, heterochromatin completely accounts for the total amount of DNA remains condensed and darkly stained throughout thepresent (PEACOCKet al. 1977b), suggesting that few, cell cycle of most cells. It occupies identical positions if any, othertypes of DNA sequences reside withinD. on homologous chromosomes and in Drosophila ac- melanogaster heterochromatin.This view was sup- counts for the proximal half of the X chromosome, ported by the discovery of junction DNA molecules the entire Y, the proximal 1/5 to 1/4 of the arms on that covalently link adjacent blocks of satellite DNA the two major autosomes, and ofmost the small fourth (BRUTLAGet al. 1977). While a few nonsatellite se- chromosome.In total, heterochromatin represents quences appear to be in heterochromatin, only trace approximately 28% of the total Drosophila genome amounts of satellite DNA are found outsidethe het- (PEACOCKet al. 1973). erochromatic regions (PEACOCKet al. 1977a; COHEN There is a striking correlation between regions of and BOWMAN1979). thegenome withlittle or nogenetic activity and Even though the molecular and structural proper- regions of heterochromatin. The DNA composition ties of heterochromatin indicate a paucity if not a of constitutive heterochromatin wouldalso argue that complete absence of gene expression, a number of little genetic activity couldoccur in these regions. genetic functions have been mapped to the hetero- Constitutive heterochromatin is greatly enriched in chromatin ofD. melanogaster (see reviewby HILLIKER, satellite DNA, which is composed of very short nu- APPELS and SCHALET1980). Thenucleolus organizer cleotide sequences present in hundreds of thousands regions in both theX and Y heterochromatin contain of copies per genome (YASMINEH and YUNIS 1969; the tandemly repeated genes for rRNA(RITOSSA and RAE 1970;JONES and ROBERTSON1970; PARDUEand SPIEGELMAN1965). Although these genes are located GALL 1970;PEACOCK et al. 1973; GALL andATHER- at the large secondary constrictions in the heterochro- TON 1974). PEACOCKet al. (1973, 1977a) have shown matin, they retain many of the properties of hetero- Genetics 120 503-517 (October, 1988) 504 G. E. MarchantG. and D. Holm chromatin when separated from the heterochromatic of recessive lethal and visible mutations allelic to the region (HILLIKER andAPPELS 1982). Male fertility in deficiencies of the heterochromatic region of chro- D. melanogaster requires the presence of six fertility mosome 2 revealed the presence of 13 nonrepetitive factors on the heterochromatic Y chromosome genes, seven to the left and six to the right of the (BROUSSEAU1960; KENNISON198 1; HAZELRIGG,FOR- centromere (HILLIKER1976). Cytological examina- NIT1 and KAUFMAN 1982; GATTI and PIMPINELLI tions of the detachment-product deficiencies in chro- 1983). Each fertility factor is involved in a specific mosome 2 indeed demonstrated that the deficiencies step in sperm development (HARDY,TOKOYASU and were restricted to the heterochromatic regions. LINDSLEY1981) and seems to code for a different However, the euchromatin-like genes shown to be protein required for sperm development and fertility in chromosome 2 heterochromatin do not seem to (GOLDSTEIN,HARDY andLINDSLEY 1982). The recov- exist in the heterochromatin of the X or Y chromo- ery of EMS-induced (WILLIAMSON1970, 1972) and some (LINDSLEY, EDINGTONand VON HALLE1960; temperature-sensitive (AYLESet al. 1973) mutations SCHALETand LEFEVRE1973; HILLIKERand APPELS of male fertility factors suggest that they are single- 1982; KENNISON1981; GATTIand PIMPINELLI1983) copy, transcribed genes. However, on the basis of an (see also review by HILLIKER,APPELS and SCHALET extensive break-point analysis, GATTIand PIMPINELLI 1980). These findings raise the possibility that heter- (1983) havesuggested that at leastsome of the Y ochromatin in D. melanogaster may be heterogeneous fertility factors may have an enormous physical size, with respect to genetic activity. Sincethe heterochro- each containing up to several thousand kilobases of matin of the sex chromosomes has a very different DNA. In addition to the six fertility factors there is a genetic composition than the heterochromatin of at specific segment on the long arm of the Y required least one of the major autosomes, it would be of for normal sperm development. Deletion of this seg- significant interest to determine if the genetic content ment results in crystal formation in primary sperma- of chromosome 3, the other major autosome, con- tocytes, but not sterility (HARDYet at. 1984; LIVAK forms to this dichotomous pattern. The results of 1984). BALDWINand SUZUKI(197 1) which introduced the Other genetic properties have been mapped to spe- technique of generating proximaldeficiencies cific regions of D. melanogaster heterochromatin, al- throughthe detachment of compound autosomes, though it is not clear whether transcribed genes are suggested that chromosome 3 heterochromatin does involved. The chromosomal regions responsible for contain essential genes. However, there was insuffi- nucleolar dominance (DURICAand KRIDER 1978) and cient information about the number, distribution, re- compensationresponse (PROCUNIERand TARTOF petitiveness and nature of genes in chromosome 3 1978) are located in the X chromosome heterochro- heterochromatin to permit a validcomparison be- matin. A segment of the X heterochromatin also in- tween the heterochromatic gene content of the two teracts with a family of recessive maternal mutations major autosomes. including abnormal oocyte (SANDLER1979,1972,1977; In the present study we analyzed over 440 recon- PARRY andSANDLER 1974; PIMPINELLIet al. 1985). stituted third chromosomes generated through the Extra copies of a specific segment of X heterochro- radiation-induced detachment of 12 different combi- matin as well as two segments of the Y, can partially nations of C(3L)and C(3R).These compound auto- compensate for the maternal mutant defect in abnor- somes were newly generated as sister-chromatid at- mal oocyte progeny (SANDLER1970; PIMPINELLIet al. tachments from a recently established isogenic-3strain 1985). Finally, elements involved in the segregation to avoid the accumulation of recessive lethals, espe- distortion (SD) phenomenon have been mapped to cially near the centromere where the frequency of the heterochromatin of chromosome 2 (GANETSKY homozygosity is verylow (PARKER1954). Some of 1977; BRITTNACHERand GANETSKY1984; SHARP, these compounds carried duplications for the proxi- HILLIKERand HOLM1985), and recently MCKEEand mal heterochromatin on the opposite arm and some LINDSLEY987) (1 report that theheterochromatic sites were heterozygous for deficiencies. Although these on the X responsible for sex chromosome pairing are properties were not known prior to recovering and very closely linked and probably identical with the analyzing the products of detachment, they provided sites required for normal sperm development and for the essential
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