The Genetic Analysis of D. melanogaster Heterochromatin Review

Field: Biochemistry, Genetics and Molecular Biology (Life Sciences)

A. J. Hilliker and R. Appels Division of Plant Industry Commonwealth Scientific and Industrial Research Organization P.O. Box 1600 Canberra City, A.C.T. 2601, Australia A. Schalet Department of Radiation Genetics State University of Leiden Wassenaarseweg 62 Leiden, The Netherlands Summary Classical, or constitutive (Brown, 1966), hetero- chromatin is a nearly ubiquitous aspect of higher eukaryotic chromosome structure and its genetic significance has been debated since its first de- scription (Heitz, 1928, 1929). This review describes genetic studies on the heterochromatin of Drosoph- ila and the perspectives they provide on the possi- ble biological role(s) of constitutive heterochroma- tin. In addition to documenting the existence of gene loci within heterochromatin, these studies pro- vide evidence for long-range interactions within the nucleus and involving heterochromatin. These in- teractions may reflect more general properties of chromatin related to the three-dimensional struc- ture of the interphase nucleus and its effects on gene expression. Introduction In Drosophila melanogaster the entire Y chromosome is heterochromatic, having a very condensed appear- ance and showing no separation of sister chromatids in late prophase of the cell cycle (Heitz, 1933; Kauf- mann, 1934; Figures 1 and 4a). The proximal half of the X chromosome and the proximal quarters of the arms of chromosomes 2 and 3 are heterochromatic and also show the property of chromatid apposition. Cytologically, heterochromatin of the X and Y chro- mosomes is divisible into regions owing to the pres- ence of secondary constrictions (reviewed by Cooper, 1959). It has been speculated that the major second- ary constrictions, in the heterochromatin of the long arm of the X and the short arm of the Y, mark the location of the ribosomal RNA genes (Ritossa, Atwood and Spiegelman, 1966) and that the non-nucleolar constrictions found on the Y are the sites of the fertility factor loci (Hilliker, 1976). Using stains such as quin- acrine-HCI, heterochromatin can be resolved further into characteristic banded regions (Holmquist, 1975; Gatti, Pimpinelli and Santini, 1976; Pimpinelli, Santini and Gatti. 1976). Heterochromatin thus has a sub- structure, as defined by cytological features, and at the DNA sequence level individual regions can be shown to have well defined arrangements of highly repeated sequence DNA (for review see Appels and Peacock, 1978). A notable difference between Drosophila hetero- chromatin and euchromatin concerns their relative replicative behavior during polytene chromosome for- mation (reviewed by Gall, 1973). During polytenization the euchromatin replicates to form characteristic bands or chromomeres which may correspond to functional genetic units (reviewed by Lefevre, 1974; Young and Judd, 1978; Hilliker et al., 1980). HOW- ever, the bulk of the mitotic heterochromatin, termed LY heterochromatin by Heitz (1934) does not replicate (Rudkin, 1969) and forms the chromocenter at which the euchromatic chromosome arms fuse. At junc- tion of the chromocenter and the chromosomal arms are poorly banded segments, termed p heterochro- matin (Heitz, 1934) which do replicate (reviewed by Gall, 1973). We consider that the p heterochromatin corresponds to mitotic proximal euchromatin and that its diffuse polytene banding is the result of its juxta- position to mitotic heterochromatin. Additional properties of Drosophila heterochromatin include late replication relative to euchromatin (Bari- gozzi et al., 1966) a feature characteristic of the heterochromatin of many species (Lima-de-Faria and Jaworska, 1968). Little or no meiotic recombination occurs in the autosomal heterochromatin of Drosoph- ila virilis (Baker, 1958) or in the Drosophila melano- gaster X chromosome (Muller and Painter, 1932; Rob- erts, 1965; Schalet and Lefevre, 1976) and autosomal (Hilliker, 1975) heterochromatin. These properties, taken together with the observations that Drosophila heterochromatin is exceedingly underreplicated dur- ing the formation of polytene chromosomes and is greatly enriched for highly repeated sequence DNA (Peacock et al., 1977). have tended to reinforce the concept that there is a lack of genetic information in heterochromatin. Our review of the genetic functions located in, or associated with, heterochromatin indi- cates that this concept is no longer tenable. Location of Genes in Chromosome 2 Heterochromatin It is critical to the subject of this review that we document the existence of genetic elements in the region of chromosome identified cytologically as heterochromatin. This has been carried out in the most detail for chromosome 2. The second chromosome is a metacentric autosome with a centromere flanked by two large heterochro- matic regions (Figure 1). The region on the left arm (2L) is approximately 20% of the prometaphase length of 2L and the region on the right arm (2R) is approxi- mately 25% of the prometaphase length of 2R. The heterochromatin-euchromatin junction of 2L is