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Of the Notch Locus in Drosophila Melanogaster

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Of the Notch Locus in Drosophila Melanogaster Heredity 61(1988)107—110 The Genetical Society of Great Britain Received 12 October 1987 Effect of transvection on the expression of the Notch locus in Drosophila melanogaster Marlitta Siren and Laboratory of Genetics, Department of Biology, Petter Portin University of Turku, SF-20500 Turku 50, Finland. The effect of different X chromosomal inversions in a heterozygous condition on the expression of the recessive lethal Abruptex mutations of the Notch locus of Drosophila melanogaster was studied by measuring quantitatively the effect of Abruptex on the number of bristles, and on wing venation. The Abruptex mutations were combined in cis with recessive mutations located in the same exon, on the one hand, and in the large intron of the locus on the other. All the inversions studied caused some suppression of the mutant bristle phenotype, and the complex inversions a suppression of the wing venation phenotype, as well. This is consistent with the hypothesis that transvection causes a reduction in the amount of the gene product, since lethal Abruptex mutations are antimorphic mutations. One short inversion caused an enhancement of the wing venation phenotype. Compounds of exon and intron mutations in cis gave similar results, which are discussed from the point of view of the enhancer hypothesis of transvection. In general, the results suggest that transvection is a general phenomenon in Drosophila melanogaster, possibly involving all loci. INTRODUCTION of the locus give similar results irrespective of whether they are located in the same exon (split, Theeffect of structural heterozygosity on the spi) or in a distally located large intron (facet- expression of genes on homologous chromosomes glossy, faa). We have previously demonstrated that was discovered and termed transvection by Lewis these mutations have an effect on Abruptex, split (1954) in the bithorax complex locus of Drosophila in general enhancing and facet-glossy suppressing melanogaster. In the bithorax locus transvection the expression of Abruptex in cis-compounds induced an enhancement of the mutant phenotype (Siren and Portin, 1984). This result will be dis- of alleles in the trans position, and was thought cussed in the light of the enhancer hypothesis of to be due to the prevention of the opposition of the transvection effect of Zachar et aL (1985). In homologous alleles (Lewis, 1954; Gelbart, 1982). general our results support the enhancer In addition to the effect at the bithorax complex hypothesis, since they suggest that transvection is (BX-C; map location 3-58.8) transvection has a general phenomenon in D. melanogaster, poss- been observed in the decapentaplegic complex ibly involving all loci. Also, the results support the (DPP-C; 2-4.0) (Gelbart, 1982) and at the white hypothesis that the transvection effect is due to a locus (w; 1—1.5) (Green, 1967; Gelbart, 1971, 1982; reduction in the amount of the gene product from Jack and Judd, 1979; Gelbart and Wu, 1982; the structurally normal homologue. Zachar et a!., 1985; Smolik-Utlaut and Gelbart, 1987). Synapsis-dependent trans regulation of gene activity has also been suggested for the MATERIALS AND METHODS salivary gland glue protein 4 (Sgs-4) gene by Korge (1981). The Abruptex (Ax, 1-30) mutations of the Notch The aim of the present study was to demon- locus make it possible to measure gene expression strate the transvection effect at the Notch (N; quantitatively since they cause missing bristles on 1-3.0) locus of D. melanogaster, and further to the head and thorax, and breaks in the wing veins. demonstrate that mutations coupled in cis with the We counted the mean numbers of missing orbital, Abruptex (Ax) mutations located in the large exon dorsocentral, and scutellar bristles; counted the 108 M. SIREN AND P. PORTIN number of wing breaks, and measured their length microscopically. The Abruptex mutations used £ I. were AxS9tslandAx59"5 which are recessive lethal pI A mutations (Weishons 1971), and antimorphic in their mode of action (Portin, 1981). The expression Figure 1 The molecular fine structure map of the Notch locus indicating the positions offa5 and spi, and the approximate of these Ax mutations was measured in females positions of Ax59"°' and Ax59'5 (designated Ax). Thin heterozygous for either a normal X chromosome lines are intronx, and heavy lines are exons. fa° is an or three different structurally mutant X chromo- insertion while api as well as Ax mutations map as a points. somes. The latter ones were In(l)FM6, Basc, and Data from Artavanis-Tsakonas et a!., 1984; Hartley et a!., 1987; Kelley eta!.,1987;Kidd et al., 1983; Kidd and Young, fn(1)Lü-2. Information on the complex rearrange- 1984. ments in In(1)FM6 and Basc can be found in Lindsley and Grell (1968). In(1)Lii-2 was kindly molecular nature of AxS9btI and Ax59"5 as well as provided by Professor K. G. Lüning (Stockholm, Sweden), and is an inversion of 50 bands between of five viable Ax mutations has been indicated the foci of white (w, 1—1.5) and curlex (cx, 1—13.6) quite recently. They map as points, and are associ- (Lüning, personal communication). The Ax muta- ated with single amino acid substitutions in the tions were investigated in simple heterozygotes, or Epidermal Growth Factor-like sequences of the they were coupled with either of two different gene product (Kelley et a!., 1987). visible mutations of the Notch locus, namely split Flies were reared on a standard Drosophi!a (spi) and facet-glossy (fa5). medium containing semolina, agar-agar, syrup, The molecular fine structure map of the Notch and both dried and fresh yeast at 25°C. locus is presented in fig. 1. In the figure the loca- The results were statistically analysed by the tions offa and spi are given as well as the approxi- analysis of variance. mate locations of Ax591'5' and Ax59"5. fa5 is a short insertion in the large intron of the locus RESULTS (Artavanis-Tsakonas eta!., 1984; Kidd and Young, 1986), while spi is a point mutation in the large Theexpression of the Abruptex phenotype in the exon of the locus (Hartley et a!., 1987). The different genotypes tested is given in table 1. All Table 1 The expression of Abruptex phenotype of different genotypes of the Notch locus involving Abruptex mutations in different combinations with split and facet-glossy mutations and heterozygous with three different X chromosomal inversions Number of missing orbital, dorsocentral, Number of wing Length of wing and scutellar bristles vein breaks vein breaks (mm) Genotype Mean±S.D. Mean±S.D. Mean±S.D. N +Ax59'8'/+ + 6-85±1-38 3-40±0-85 0-43±0-09 47 +AxSSLSI/Jn(1)FM6 4-49±122 115±077 0-10±008 71 +Ax59'8'/ Basc 3-900-90 1-930-31 0-23 +0-06 70 +AxssLsl/1n(1)Lu2 5-36±1-22 3-69±0-74 0-51±0-18 73 +Ax59"5/+ + 6-62±0-86 318±072 037±008 45 +Ax59"5/In(1)FM6 4-13± 1-19 1-21±0-69 0-09±0-06 72 +Ax59"5/Basc 3-60± 1-12 1-89±0-36 018±0-08 72 +Ax59"/In(l)Lü-2 4-68± 1-04 3-60±0-72 0-47±0-16 75 fa°Ax"5/+ + 4-82±1-05 162±0-65 011±0-06 45 fa°Ax59"5/Jn(1)FM6 2-20±0-57 0-00±0-00 0-00±0-00 74 faAx59"5/Basc 024±053 019±0-45 0-01±0-03 83 faAx59"5/Jn(I)Lü-2 2-69± 1-06 2-11 0-25±0-08 71 sp1Ax5958'/+ + 13-25±0-96 4-00±0-00 067±0-09 48 apI Ax59"'/Jn (1)FM6 11-58± 1-15 1-86±0-57 0-23±0-04 71 sp!Ax59"'/Basc 12-21±0-97 1-93±0-29 0-17±0-05 86 splAx59"'/In(1)Lü-2 12-86±0-99 4-27±0-50 0-96±0-21 77 spIAx59"5/++ 13-43±0-78 3-83±0-44 0-52±0-09 46 sp!Ax59"5/In(1)FM6 11-51±1-30 1-86±0-45 0-26±0-08 77 sp!Ax59'5/Basc 11-25±1-07 1-95±0-22 0-23±0-06 83 api Ax59"5/In(1)Lu-2 13-10±0-82 4-17±0-52 078±011 77 TRANSVECTION IN DROSOPHILA 109 inversions tested caused some suppression of the Zachar eta!. (1985) suggested that the w" element mutant bristle phenotype in heterozygous condi- activates transcription from the wL transposon tion with all the Notch compounds tested. The unique segment promoter. complex X chromosomal inversions (In(1)FM6 Like w'', fa5 is also an insertion, although and Basc) also caused a suppression of the mutant in this case inside the locus in an intron, while spi wing venation phenotype in all genotypes tested, is a point mutation in the same exon where Ax is while In(1)Lü-2 caused an enhancement of the located. Earlier we have observed that in general wing venation phenotype. This latter exceptional fa suppresses and spi enhances the expression of observation is probably due to the vicinity of the Abruptex in cis compounds (Siren and Portin, curlex (cx) gene of the proximal break point of 1984) (see also table 1). Despite this, they have a In(l)Lü-2. Curlex affects the development of the similar behaviour in the transvection effect. There- wings (see Lindsley and Grell, 1968). All differen- fore, our results might be in contradiction to the ces were statically significant.
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