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. 1994 Mar;136(3):913–926. doi: 10.1093/genetics/136.3.913

Effects of the Maleless Mutation on X and Autosomal Gene Expression in Drosophila Melanogaster

J C Hiebert 1, J A Birchler 1
PMCID: PMC1205896  PMID: 8005444

Abstract

The mutational effect of the maleless (mle) gene in Drosophila has been reexamined. Earlier work had suggested that mle along with other male-lethal genes was responsible for hypertranscription of the X chromosome in males to bring about dosage compensation. Prompted by studies on dosage sensitive regulatory genes, we tested for effects of mle(ts) on the phenotypes of 16 X or autosomal mutations in adult escapers of lethality. In third instar larvae, prior to the major lethal phase of mle, we examined activities of 6 X or autosomally encoded enzymes, steady state mRNA levels of 15 X-linked or autosomal genes and transcripts from two large genomic segments derived from either the X or from chromosome 2 and present in yeast artificial chromosomes. In contrast to the previously hypothesized role, we detected pronounced effects of mle on the expression of both X-linked and autosomal loci such that a large proportion of the tested genes were increased in expression, while only two X-linked loci were reduced. The most prevalent consequence was an increase of autosomal gene expression, which can explain previously observed reduced X:autosome transcription ratios. These observations suggest that if mle plays a role in the discrimination of the X and the autosomes, it may do so by modification of the effects of dosage sensitive regulatory genes.

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Selected References

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  1. Baker B. S. Sex in flies: the splice of life. Nature. 1989 Aug 17;340(6234):521–524. doi: 10.1038/340521a0. [DOI] [PubMed] [Google Scholar]
  2. Bialojan S., Falkenburg D., Renkawitz-Pohl R. Characterization and developmental expression of beta tubulin genes in Drosophila melanogaster. EMBO J. 1984 Nov;3(11):2543–2548. doi: 10.1002/j.1460-2075.1984.tb02170.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Birchler J. A. Expression of cis-regulatory mutations of the white locus in metafemales of Drosophila melanogaster. Genet Res. 1992 Feb;59(1):11–18. doi: 10.1017/s0016672300030123. [DOI] [PubMed] [Google Scholar]
  4. Birchler J. A., Hiebert J. C. Interaction of the Enhancer of white-apricot with transposable element alleles at the white locus in Drosophila melanogaster. Genetics. 1989 May;122(1):129–138. doi: 10.1093/genetics/122.1.129. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Birchler J. A., Hiebert J. C., Paigen K. Analysis of autosomal dosage compensation involving the alcohol dehydrogenase locus in Drosophila melanogaster. Genetics. 1990 Mar;124(3):679–686. [PMC free article] [PubMed] [Google Scholar]
  6. Birchler J. A., Newton K. J. Modulation of protein levels in chromosomal dosage series of maize: the biochemical basis of aneuploid syndromes. Genetics. 1981 Oct;99(2):247–266. doi: 10.1093/genetics/99.2.247. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Birchler J. A. The genetic basis of dosage compensation of alcohol dehydrogenase-1 in maize. Genetics. 1981 Mar;97(3-4):625–637. doi: 10.1093/genetics/97.3-4.625. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Breen T. R., Lucchesi J. C. Analysis of the dosage compensation of a specific transcript in Drosophila melanogaster. Genetics. 1986 Mar;112(3):483–491. doi: 10.1093/genetics/112.3.483. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Charlesworth B. The evolution of sex chromosomes. Science. 1991 Mar 1;251(4997):1030–1033. doi: 10.1126/science.1998119. [DOI] [PubMed] [Google Scholar]
  10. Church G. M., Gilbert W. Genomic sequencing. Proc Natl Acad Sci U S A. 1984 Apr;81(7):1991–1995. doi: 10.1073/pnas.81.7.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Cline T. W. Autoregulatory functioning of a Drosophila gene product that establish es and maintains the sexually determined state. Genetics. 1984 Jun;107(2):231–277. doi: 10.1093/genetics/107.2.231. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Dawid I. B., Wellauer P. K., Long E. O. Ribosomal DNA in Drosophila melanogaster. I. Isolation and characterization of cloned fragments. J Mol Biol. 1978 Dec 25;126(4):749–768. doi: 10.1016/0022-2836(78)90018-9. [DOI] [PubMed] [Google Scholar]
  13. Detwiler C., MacIntyre R. A genetic and developmental analysis of an acid deoxyribonuclease in Drosophila melanogaster. Biochem Genet. 1978 Dec;16(11-12):1113–1134. doi: 10.1007/BF00484532. [DOI] [PubMed] [Google Scholar]
  14. Devlin R. H., Bingham B., Wakimoto B. T. The organization and expression of the light gene, a heterochromatic gene of Drosophila melanogaster. Genetics. 1990 May;125(1):129–140. doi: 10.1093/genetics/125.1.129. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Driever W., Nüsslein-Volhard C. The bicoid protein is a positive regulator of hunchback transcription in the early Drosophila embryo. Nature. 1989 Jan 12;337(6203):138–143. doi: 10.1038/337138a0. [DOI] [PubMed] [Google Scholar]
  16. Feinberg A. P., Vogelstein B. A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity. Anal Biochem. 1983 Jul 1;132(1):6–13. doi: 10.1016/0003-2697(83)90418-9. [DOI] [PubMed] [Google Scholar]
  17. Fitz-Earle M., Holm D. G. Exploring the Potential of Compound;free-Arm Combinations of Chromosome 2 in DROSOPHILA MELANOGASTER for Insect Control and the Survival to Pupae of Whole-Arm Trisomies. Genetics. 1978 Jul;89(3):499–510. doi: 10.1093/genetics/89.3.499. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Fukunaga A., Tanaka A., Oishi K. Maleless, a recessive autosomal mutant of Drosophila melanogaster that specifically kills male zygotes. Genetics. 1975 Sep;81(1):135–141. doi: 10.1093/genetics/81.1.135. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Ganguly R., Ganguly N., Manning J. E. Isolation and characterization of the glucose-6-phosphate dehydrogenase gene of Drosophila melanogaster. Gene. 1985;35(1-2):91–101. doi: 10.1016/0378-1119(85)90161-1. [DOI] [PubMed] [Google Scholar]
  20. Garza D., Ajioka J. W., Burke D. T., Hartl D. L. Mapping the Drosophila genome with yeast artificial chromosomes. Science. 1989 Nov 3;246(4930):641–646. doi: 10.1126/science.2510296. [DOI] [PubMed] [Google Scholar]
  21. Gergen J. P. Dosage Compensation in Drosophila: Evidence That daughterless and Sex-lethal Control X Chromosome Activity at the Blastoderm Stage of Embryogenesis. Genetics. 1987 Nov;117(3):477–485. doi: 10.1093/genetics/117.3.477. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Geyer P. K., Corces V. G. Separate regulatory elements are responsible for the complex pattern of tissue-specific and developmental transcription of the yellow locus in Drosophila melanogaster. Genes Dev. 1987 Nov;1(9):996–1004. doi: 10.1101/gad.1.9.996. [DOI] [PubMed] [Google Scholar]
  23. Goldberg M. L., Paro R., Gehring W. J. Molecular cloning of the white locus region of Drosophila melanogaster using a large transposable element. EMBO J. 1982;1(1):93–98. doi: 10.1002/j.1460-2075.1982.tb01130.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Gorman M., Kuroda M. I., Baker B. S. Regulation of the sex-specific binding of the maleless dosage compensation protein to the male X chromosome in Drosophila. Cell. 1993 Jan 15;72(1):39–49. doi: 10.1016/0092-8674(93)90048-u. [DOI] [PubMed] [Google Scholar]
  25. Hall J. C., Kankel D. R. Genetics of acetylcholinesterase in Drosophila melanogaster. Genetics. 1976 Jul;83(3 PT2):517–535. [PMC free article] [PubMed] [Google Scholar]
  26. Hazelrigg T., Levis R., Rubin G. M. Transformation of white locus DNA in drosophila: dosage compensation, zeste interaction, and position effects. Cell. 1984 Feb;36(2):469–481. doi: 10.1016/0092-8674(84)90240-x. [DOI] [PubMed] [Google Scholar]
  27. Hiebert J. C., Birchler J. A. Dosage compensation of the copia retrotransposon in Drosophila melanogaster. Genetics. 1992 Mar;130(3):539–545. doi: 10.1093/genetics/130.3.539. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Hodgetts R. B. The response of dopa decarboxylase activity to variations in gene dosage in Drosophila: a possible location of the structural gene. Genetics. 1975 Jan;79(1):45–54. doi: 10.1093/genetics/79.1.45. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Jiang J., Levine M. Binding affinities and cooperative interactions with bHLH activators delimit threshold responses to the dorsal gradient morphogen. Cell. 1993 Mar 12;72(5):741–752. doi: 10.1016/0092-8674(93)90402-c. [DOI] [PubMed] [Google Scholar]
  30. Kongsuwan K., Yu Q., Vincent A., Frisardi M. C., Rosbash M., Lengyel J. A., Merriam J. A Drosophila Minute gene encodes a ribosomal protein. Nature. 1985 Oct 10;317(6037):555–558. doi: 10.1038/317555a0. [DOI] [PubMed] [Google Scholar]
  31. Lehrach H., Diamond D., Wozney J. M., Boedtker H. RNA molecular weight determinations by gel electrophoresis under denaturing conditions, a critical reexamination. Biochemistry. 1977 Oct 18;16(21):4743–4751. doi: 10.1021/bi00640a033. [DOI] [PubMed] [Google Scholar]
  32. Levis R., Hazelrigg T., Rubin G. M. Separable cis-acting control elements for expression of the white gene of Drosophila. EMBO J. 1985 Dec 16;4(13A):3489–3499. doi: 10.1002/j.1460-2075.1985.tb04108.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Lucchesi J. C., Rawls J. M., Jr, Maroni G. Gene dosage compensation in metafemales (3X;2A) of Drosophila. Nature. 1974 Apr 12;248(449):564–567. doi: 10.1038/248564a0. [DOI] [PubMed] [Google Scholar]
  34. McNabb S. L., Beckendorf S. K. Cis-acting sequences which regulate expression of the Sgs-4 glue protein gene of Drosophila. EMBO J. 1986 Sep;5(9):2331–2340. doi: 10.1002/j.1460-2075.1986.tb04501.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Messmer S., Franke A., Paro R. Analysis of the functional role of the Polycomb chromo domain in Drosophila melanogaster. Genes Dev. 1992 Jul;6(7):1241–1254. doi: 10.1101/gad.6.7.1241. [DOI] [PubMed] [Google Scholar]
  36. Moore G. P., Sullivan D. T. Biochemical and genetic characterization of kynurenine formamidase from Drosophila melanogaster. Biochem Genet. 1978 Aug;16(7-8):619–634. doi: 10.1007/BF00484718. [DOI] [PubMed] [Google Scholar]
  37. Mukherjee A. S., Beermann W. Synthesis of ribonucleic acid by the X-chromosomes of Drosophila melanogaster and the problem of dosage compensation. Nature. 1965 Aug 14;207(998):785–786. doi: 10.1038/207785a0. [DOI] [PubMed] [Google Scholar]
  38. Muskavitch M. A., Hogness D. S. An expandable gene that encodes a Drosophila glue protein is not expressed in variants lacking remote upstream sequences. Cell. 1982 Jul;29(3):1041–1051. doi: 10.1016/0092-8674(82)90467-6. [DOI] [PubMed] [Google Scholar]
  39. O'Brien S. J., Gethmann R. C. Segmental aneuploidy as a probe for structural genes in Drosophila: mitochondrial membrane enzymes. Genetics. 1973 Sep;75(1):155–167. doi: 10.1093/genetics/75.1.155. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Oliver M. J., Huber R. E., Williamson J. H. Genetic and biochemical aspects of trehalase from Drosophila melanogaster. Biochem Genet. 1978 Oct;16(9-10):927–940. doi: 10.1007/BF00483744. [DOI] [PubMed] [Google Scholar]
  41. Palmer M. J., Mergner V. A., Richman R., Manning J. E., Kuroda M. I., Lucchesi J. C. The male-specific lethal-one (msl-1) gene of Drosophila melanogaster encodes a novel protein that associates with the X chromosome in males. Genetics. 1993 Jun;134(2):545–557. doi: 10.1093/genetics/134.2.545. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Raha S., Merante F., Proteau G., Reed J. K. Simultaneous isolation of total cellular RNA and DNA from tissue culture cells using phenol and lithium chloride. Genet Anal Tech Appl. 1990 Nov;7(7):173–177. doi: 10.1016/0735-0651(90)90022-8. [DOI] [PubMed] [Google Scholar]
  43. Rawls J. M., Jr, Lucchesi J. C. Regulation of enzyme activities in Drosophila. I. The detection of regulatory loci by gene dosage responses. Genet Res. 1974 Aug;24(1):59–72. doi: 10.1017/s001667230001507x. [DOI] [PubMed] [Google Scholar]
  44. Reichert G. H. Two-dimensional gel analysis of proteins from mouse fetuses with trisomy 19 after DEAE-Sepharose chromatography. Genet Res. 1986 Jun;47(3):193–197. doi: 10.1017/s0016672300023120. [DOI] [PubMed] [Google Scholar]
  45. Sabl J. F., Birchler J. A. Dosage dependent modifiers of white alleles in Drosophila melanogaster. Genet Res. 1993 Aug;62(1):15–22. doi: 10.1017/s0016672300031517. [DOI] [PubMed] [Google Scholar]
  46. Sass H., Meselson M. Dosage compensation of the Drosophila pseudoobscura Hsp82 gene and the Drosophila melanogaster Adh gene at ectopic sites in D. melanogaster. Proc Natl Acad Sci U S A. 1991 Aug 1;88(15):6795–6799. doi: 10.1073/pnas.88.15.6795. [DOI] [PMC free article] [PubMed] [Google Scholar]
  47. Sauer F., Jäckle H. Dimerization and the control of transcription by Krüppel. Nature. 1993 Jul 29;364(6436):454–457. doi: 10.1038/364454a0. [DOI] [PubMed] [Google Scholar]
  48. Scott M. J., Lucchesi J. C. Structure and expression of the Drosophila melanogaster gene encoding 6-phosphogluconate dehydrogenase. Gene. 1991 Dec 30;109(2):177–183. doi: 10.1016/0378-1119(91)90607-d. [DOI] [PubMed] [Google Scholar]
  49. Searles L. L., Voelker R. A. Molecular characterization of the Drosophila vermilion locus and its suppressible alleles. Proc Natl Acad Sci U S A. 1986 Jan;83(2):404–408. doi: 10.1073/pnas.83.2.404. [DOI] [PMC free article] [PubMed] [Google Scholar]
  50. Segraves W. A., Louis C., Tsubota S., Schedl P., Rawls J. M., Jarry B. P. The rudimentary locus of Drosophila melanogaster. J Mol Biol. 1984 May 5;175(1):1–17. doi: 10.1016/0022-2836(84)90441-8. [DOI] [PubMed] [Google Scholar]
  51. Skripsky T., Lucchesi J. C. Intersexuality resulting from the interaction of sex-specific lethal mutations in Drosophila melanogaster. Dev Biol. 1982 Nov;94(1):153–162. doi: 10.1016/0012-1606(82)90078-1. [DOI] [PubMed] [Google Scholar]
  52. Smith P. D., Lucchesi J. C. The role of sexuality in dosage compensation in Drosophila. Genetics. 1969 Mar;61(3):607–618. doi: 10.1093/genetics/61.3.607. [DOI] [PMC free article] [PubMed] [Google Scholar]
  53. Spradling A. C., Rubin G. M. The effect of chromosomal position on the expression of the Drosophila xanthine dehydrogenase gene. Cell. 1983 Aug;34(1):47–57. doi: 10.1016/0092-8674(83)90135-6. [DOI] [PubMed] [Google Scholar]
  54. Stewart B. R., Merriam J. R. Regulation of gene activity by dosage compensation at the chromosomal level in drosophila. Genetics. 1975 Apr;79(4):635–647. doi: 10.1093/genetics/79.4.635. [DOI] [PMC free article] [PubMed] [Google Scholar]
  55. Strobel E., Pelling C., Arnheim N. Incomplete dosage compensation in an evolving Drosophila sex chromosome. Proc Natl Acad Sci U S A. 1978 Feb;75(2):931–935. doi: 10.1073/pnas.75.2.931. [DOI] [PMC free article] [PubMed] [Google Scholar]
  56. Struhl G., Struhl K., Macdonald P. M. The gradient morphogen bicoid is a concentration-dependent transcriptional activator. Cell. 1989 Jun 30;57(7):1259–1273. doi: 10.1016/0092-8674(89)90062-7. [DOI] [PubMed] [Google Scholar]
  57. Tearle R. G., Belote J. M., McKeown M., Baker B. S., Howells A. J. Cloning and characterization of the scarlet gene of Drosophila melanogaster. Genetics. 1989 Jul;122(3):595–606. doi: 10.1093/genetics/122.3.595. [DOI] [PMC free article] [PubMed] [Google Scholar]
  58. Warrior R., Levine M. Dose-dependent regulation of pair-rule stripes by gap proteins and the initiation of segment polarity. Development. 1990 Nov;110(3):759–767. doi: 10.1242/dev.110.3.759. [DOI] [PubMed] [Google Scholar]
  59. Whatley S. A., Hall C., Davison A. N., Lim L. Alterations in the relative amounts of specific mRNA species in the developing human brain in Down's syndrome. Biochem J. 1984 May 15;220(1):179–187. doi: 10.1042/bj2200179. [DOI] [PMC free article] [PubMed] [Google Scholar]
  60. Yim J. J., Grell E. H., Jacobson K. B. Mechanism of suppression in Drosophila: control of sepiapterin synthase at the purple locus. Science. 1977 Dec 16;198(4322):1168–1170. doi: 10.1126/science.412253. [DOI] [PubMed] [Google Scholar]
  61. von Kalm L., Weaver J., DeMarco J., MacIntyre R. J., Sullivan D. T. Structural characterization of the alpha-glycerol-3-phosphate dehydrogenase-encoding gene of Drosophila melanogaster. Proc Natl Acad Sci U S A. 1989 Jul;86(13):5020–5024. doi: 10.1073/pnas.86.13.5020. [DOI] [PMC free article] [PubMed] [Google Scholar]

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