genetic dosage compensation


Summary: Genetic mechanisms that allow GENES to be expressed at a similar level irrespective of their GENE DOSAGE. This term is usually used in discussing genes that lie on the SEX CHROMOSOMES. Because the sex chromosomes are only partially homologous, there is a different copy number, i.e., dosage, of these genes in males vs. females. In DROSOPHILA, dosage compensation is accomplished by hypertranscription of genes located on the X CHROMOSOME. In mammals, dosage compensation of X chromosome genes is accomplished by random X CHROMOSOME INACTIVATION of one of the two X chromosomes in the female.

Top Publications

  1. Zha X, Xia Q, Duan J, Wang C, He N, Xiang Z. Dosage analysis of Z chromosome genes using microarray in silkworm, Bombyx mori. Insect Biochem Mol Biol. 2009;39:315-21 pubmed publisher
    ..These results provide useful clues to further understanding roles of dosage of Z chromosome and some Z-linked sexual differences in silkworms. ..
  2. Gelbart M, Larschan E, Peng S, Park P, Kuroda M. Drosophila MSL complex globally acetylates H4K16 on the male X chromosome for dosage compensation. Nat Struct Mol Biol. 2009;16:825-32 pubmed publisher
  3. Grimaud C, Becker P. The dosage compensation complex shapes the conformation of the X chromosome in Drosophila. Genes Dev. 2009;23:2490-5 pubmed publisher
    ..We propose that nuclear organization of HAS is central to the faithful distribution of the DCC along the X chromosome. ..
  4. Csankovszki G, Collette K, Spahl K, Carey J, Snyder M, Petty E, et al. Three distinct condensin complexes control C. elegans chromosome dynamics. Curr Biol. 2009;19:9-19 pubmed publisher
  5. Jans J, Gladden J, Ralston E, Pickle C, Michel A, Pferdehirt R, et al. A condensin-like dosage compensation complex acts at a distance to control expression throughout the genome. Genes Dev. 2009;23:602-18 pubmed publisher
    ..DCC disruption causes opposite effects on expression of X and autosomal genes. The DCC thus acts at a distance to impact expression throughout the genome. ..
  6. Gallach M, Arnau V, Aldecoa R, Marín I. A sequence motif enriched in regions bound by the Drosophila dosage compensation complex. BMC Genomics. 2010;11:169 pubmed publisher
  7. Ercan S, Lieb J. C. elegans dosage compensation: a window into mechanisms of domain-scale gene regulation. Chromosome Res. 2009;17:215-27 pubmed publisher
    ..We discuss how condensin-like complexes may be targeted to specific chromosomal locations for performance of their functions. ..
  8. Gelbart M, Kuroda M. Drosophila dosage compensation: a complex voyage to the X chromosome. Development. 2009;136:1399-410 pubmed publisher
    ..This review will discuss the relative contributions of sequence elements and transcriptional marks to the complete pattern of MSL complex binding. ..
  9. Gorchakov A, Alekseyenko A, Kharchenko P, Park P, Kuroda M. Long-range spreading of dosage compensation in Drosophila captures transcribed autosomal genes inserted on X. Genes Dev. 2009;23:2266-71 pubmed publisher
    ..We conclude that a long-sought specific DNA sequence within X-linked genes is not obligatory for MSL binding. Instead, linkage and transcription play the pivotal roles in MSL targeting irrespective of gene origin and DNA sequence. ..

More Information


  1. Naurin S, Hansson B, Bensch S, Hasselquist D. Why does dosage compensation differ between XY and ZW taxa?. Trends Genet. 2010;26:15-20 pubmed publisher
    ..These patterns and processes contrast with those acting on genes on the X chromosome in XY species, and might help explain the discrepancies in the degree of sex-biased gene expression and dosage compensation in XY and ZW systems. ..
  2. Vicoso B, Charlesworth B. The deficit of male-biased genes on the D. melanogaster X chromosome is expression-dependent: a consequence of dosage compensation?. J Mol Evol. 2009;68:576-83 pubmed publisher
    ..melanogaster and to measure their expression levels. This is consistent with the idea that limitations in transcription rates may prevent male-biased genes from accumulating on the X chromosome. ..
  3. Mank J. The W, X, Y and Z of sex-chromosome dosage compensation. Trends Genet. 2009;25:226-33 pubmed publisher
    ..These findings warrant a re-examination of the evolutionary forces underlying dosage compensation. ..
  4. Zhang Y, Oliver B. An evolutionary consequence of dosage compensation on Drosophila melanogaster female X-chromatin structure?. BMC Genomics. 2010;11:6 pubmed publisher
    ..We suggest that the differences between the X chromosomes and autosomes in females are a consequence of mechanisms that have evolved to ensure sufficient X chromosome expression in the soma of males. ..
  5. Blauwkamp T, Csankovszki G. Two classes of dosage compensation complex binding elements along Caenorhabditis elegans X chromosomes. Mol Cell Biol. 2009;29:2023-31 pubmed publisher
    ..These results suggest that two distinct classes of DCC-binding elements facilitate recruitment and spreading of the DCC along the X chromosome. ..
  6. Yin S, Deng W, Zheng H, Zhang Z, Hu L, Kong X. Evidence that the nonsense-mediated mRNA decay pathway participates in X chromosome dosage compensation in mammals. Biochem Biophys Res Commun. 2009;383:378-82 pubmed publisher
    ..Our results identify NMD as a post-transcription-level regulatory mechanism that contributes to the observed fine-tuning of X chromosome dosage compensation in mammals. ..
  7. Cottrell C, Sommer A, Wenger G, Bullard S, Busch T, Krahn K, et al. Atypical X-chromosome inactivation in an X;1 translocation patient demonstrating Xq28 functional disomy. Am J Med Genet A. 2009;149A:408-14 pubmed publisher
    ..As a result, the pattern of XCI is opposite that of the expected for an X;autosome translocation. Therefore, we suggest the phenotypic abnormalities found in the patient are a result of functional disomy in the Xq28 region. ..
  8. Brosnan C, Voinnet O. The long and the short of noncoding RNAs. Curr Opin Cell Biol. 2009;21:416-25 pubmed publisher
    ..Different small RNA classes regulate diverse processes such as transposon and virus suppression, as well as many key developmental processes. ..
  9. Prothero K, Stahl J, Carrel L. Dosage compensation and gene expression on the mammalian X chromosome: one plus one does not always equal two. Chromosome Res. 2009;17:637-48 pubmed publisher
    ..Moreover, escape genes give insight into how X chromosome inactivation is spread and maintained on the X. ..
  10. Menon D, Meller V. Imprinting of the Y chromosome influences dosage compensation in roX1 roX2 Drosophila melanogaster. Genetics. 2009;183:811-20 pubmed publisher
    ..We believe that the Y chromosome is likely to act through modulation of a process that is defective in roX1 roX2 mutants: X chromosome recognition or chromatin modification by the MSL complex...
  11. Petty E, Collette K, Cohen A, Snyder M, Csankovszki G. Restricting dosage compensation complex binding to the X chromosomes by H2A.Z/HTZ-1. PLoS Genet. 2009;5:e1000699 pubmed publisher
    ..We propose a model in which HTZ-1, directly or indirectly, serves to restrict the dosage compensation complex to the X chromosome by acting as or regulating the activity of an autosomal repellant. ..
  12. Hallacli E, Akhtar A. X chromosomal regulation in flies: when less is more. Chromosome Res. 2009;17:603-19 pubmed publisher
    ..Future studies integrating these aspects promise to shed more light into this epigenetic phenomenon. ..
  13. Meyer B. Targeting X chromosomes for repression. Curr Opin Genet Dev. 2010;20:179-89 pubmed publisher
    ..The reshuffling of interchangeable molecular parts creates independent machines with similar architecture but distinct biological functions. ..
  14. Hargitai B, Kutnyánszky V, Blauwkamp T, Stetak A, Csankovszki G, Takacs Vellai K, et al. xol-1, the master sex-switch gene in C. elegans, is a transcriptional target of the terminal sex-determining factor TRA-1. Development. 2009;136:3881-7 pubmed publisher
    ..These data imply the existence of a regulatory feedback loop within the C. elegans sex-determination and dosage-compensation cascade that ensures the accurate dose of X-linked genes in cells destined to adopt hermaphrodite fate. ..
  15. Rens W, Wallduck M, Lovell F, Ferguson Smith M, Ferguson Smith A. Epigenetic modifications on X chromosomes in marsupial and monotreme mammals and implications for evolution of dosage compensation. Proc Natl Acad Sci U S A. 2010;107:17657-62 pubmed publisher
    ..In comparison to the marsupial, the monotreme exhibited no epigenetic differences between homologous X chromosomes, suggesting the absence of a dosage compensation process comparable to that in therians...
  16. van den Berg I, Laven J, Stevens M, Jonkers I, Galjaard R, Gribnau J, et al. X chromosome inactivation is initiated in human preimplantation embryos. Am J Hum Genet. 2009;84:771-9 pubmed publisher
    ..These findings indicate that XCI is initiated in female human preimplantation-stage embryos and suggest that preimplantation dosage compensation is evolutionarily conserved in placental mammals. ..
  17. Busque L, Paquette Y, Provost S, Roy D, Levine R, Mollica L, et al. Skewing of X-inactivation ratios in blood cells of aging women is confirmed by independent methodologies. Blood. 2009;113:3472-4 pubmed publisher
    ..This confirms that the skewing of XCI ratio seen in blood cells of aging women is a bona fide and robust biologic phenomenon. ..
  18. London S, Itoh Y, Lance V, Wise P, Ekanayake P, Oyama R, et al. Neural expression and post-transcriptional dosage compensation of the steroid metabolic enzyme 17beta-HSD type 4. BMC Neurosci. 2010;11:47 pubmed publisher
    ..Our results demonstrate that the HSD17B4 gene is expressed and active in the zebra finch brain as an E2 metabolizing enzyme, but that dosage compensation of this Z-linked gene may occur via post-transcriptional mechanisms. ..
  19. Agrelo R, Wutz A. X inactivation and disease. Semin Cell Dev Biol. 2010;21:194-200 pubmed publisher
    ..This dosage-compensation mechanism is based on the long functional Xist RNA. Here, we review our understanding of dosage compensation and Xist function in the context of disease. ..
  20. Prince E, Kirkland D, Demuth J. Hyperexpression of the X chromosome in both sexes results in extensive female bias of X-linked genes in the flour beetle. Genome Biol Evol. 2010;2:336-46 pubmed publisher
  21. Laverty C, Lucci J, Akhtar A. The MSL complex: X chromosome and beyond. Curr Opin Genet Dev. 2010;20:171-8 pubmed publisher
    ..A comparison of Drosophila and mammalian systems reveals intriguing parallels in MOF behavior, and highlights the multidisciplinary nature of this enzyme. ..
  22. Vicoso B, Bachtrog D. Progress and prospects toward our understanding of the evolution of dosage compensation. Chromosome Res. 2009;17:585-602 pubmed publisher
    ..Finally, we discuss how dosage compensation systems can also influence the evolution of well-established sex chromosomes. ..
  23. Mank J, Vicoso B, Berlin S, Charlesworth B. Effective population size and the Faster-X effect: empirical results and their interpretation. Evolution. 2010;64:663-74 pubmed publisher
    ..Our results suggest that differences in effective population size and mechanisms of dosage compensation may influence the perceived extent of Faster-X evolution, and help to explain several clade-specific patterns that we observe. ..
  24. Yin S, Wang P, Deng W, Zheng H, Hu L, Hurst L, et al. Dosage compensation on the active X chromosome minimizes transcriptional noise of X-linked genes in mammals. Genome Biol. 2009;10:R74 pubmed publisher
    ..Given the coupling between expression level and noise on the X-chromosome, we suggest that part of the selective advantage of dosage compensation is noise abatement of X-linked genes. ..
  25. Bachtrog D, Toda N, Lockton S. Dosage compensation and demasculinization of X chromosomes in Drosophila. Curr Biol. 2010;20:1476-81 pubmed publisher
  26. Schoenmakers S, Wassenaar E, Hoogerbrugge J, Laven J, Grootegoed J, Baarends W. Female meiotic sex chromosome inactivation in chicken. PLoS Genet. 2009;5:e1000466 pubmed publisher
    ..It also indicates the presence of an evolutionary force that drives meiotic sex chromosome inactivation independent of the final achievement of synapsis. ..
  27. Gladstein N, McKeon M, Horabin J. Requirement of male-specific dosage compensation in Drosophila females--implications of early X chromosome gene expression. PLoS Genet. 2010;6:e1001041 pubmed publisher
    ..Our data suggest that before the female state is set, the ground state is male and female X chromosome expression is elevated. Females thus utilize the male dosage compensation process to amplify the signal which determines their fate. ..
  28. Melamed E, Arnold A. The role of LINEs and CpG islands in dosage compensation on the chicken Z chromosome. Chromosome Res. 2009;17:727-36 pubmed publisher
    ..Our results suggest that CpG islands are not randomly distributed on the Z chromosome and may influence Z gene dosage compensation status. ..
  29. Prestel M, Feller C, Straub T, Mitlöhner H, Becker P. The activation potential of MOF is constrained for dosage compensation. Mol Cell. 2010;38:815-26 pubmed publisher
  30. Vermaak D, Bayes J, Malik H. A surrogate approach to study the evolution of noncoding DNA elements that organize eukaryotic genomes. J Hered. 2009;100:624-36 pubmed publisher
    ..These insights also help to explain why the same elements (e.g., centromeres and replication origins), which are so complex in some eukaryotic genomes, can be simple and well defined in other where similar conflicts do not exist. ..
  31. Bredel M, Scholtens D, Harsh G, Bredel C, Chandler J, Renfrow J, et al. A network model of a cooperative genetic landscape in brain tumors. JAMA. 2009;302:261-75 pubmed publisher
    ..These mutations, which are likely due to nonrandom selection of a distinct genetic landscape during gliomagenesis, are associated with patient prognosis. ..
  32. Sun X, Birchler J. Interaction study of the male specific lethal (MSL) complex and trans-acting dosage effects in metafemales of Drosophila melanogaster. Cytogenet Genome Res. 2009;124:298-311 pubmed publisher
    ..There is a lower autosomal level of histone acetylation compared to the normal metafemales, suggesting a nullifying effect on the negative dosage effect of the X chromosome as previously hypothesized to occur in normal males. ..
  33. Zhang Y, Malone J, Powell S, Periwal V, Spana E, MacAlpine D, et al. Expression in aneuploid Drosophila S2 cells. PLoS Biol. 2010;8:e1000320 pubmed publisher
    ..Our data indicate that expression dosage compensation dampens the effect of altered DNA copy number genome-wide. For the X chromosome, compensation includes fixed and dose-dependent components. ..
  34. Birchler J, Yao H, Chudalayandi S. Biological consequences of dosage dependent gene regulatory systems. Biochim Biophys Acta. 2007;1769:422-8 pubmed
    ..In this article we will summarize the evidence for this potential synthesis. ..
  35. Zacchi L, Selmecki A, Berman J, Davis D. Low dosage of histone H4 leads to growth defects and morphological changes in Candida albicans. PLoS ONE. 2010;5:e10629 pubmed publisher
    ..This is the first study of a core nucleosomal histone in C. albicans, and constitutes the prelude to future, more detailed research on the function of histone H4 in this important fungal pathogen. ..
  36. Park C, Ahn S, Bloom J, Lin A, Wang R, Wu T, et al. Fine mapping of regulatory loci for mammalian gene expression using radiation hybrids. Nat Genet. 2008;40:421-9 pubmed publisher
    ..Further, this work identifies 2,761 trans ceQTLs harboring no known genes, and provides evidence for a mode of gene expression autoregulation specific to the X chromosome. ..
  37. Acar M, Pando B, Arnold F, Elowitz M, van Oudenaarden A. A general mechanism for network-dosage compensation in gene circuits. Science. 2010;329:1656-60 pubmed publisher
    ..This mechanism of network-dosage invariance could represent a general design for gene network structure in cells. ..
  38. Xiong Y, Chen X, Chen Z, Wang X, Shi S, Wang X, et al. RNA sequencing shows no dosage compensation of the active X-chromosome. Nat Genet. 2010;42:1043-7 pubmed publisher
    ..Together, our findings reject Ohno’s hypothesis, necessitating a major revision of the current model of dosage compensation in the evolution of sex chromosomes. ..
  39. Zhang S, Mathur S, Hattem G, Tassy O, Pourquie O. Sex-dimorphic gene expression and ineffective dosage compensation of Z-linked genes in gastrulating chicken embryos. BMC Genomics. 2010;11:13 pubmed publisher
    ..These data also suggest a potential role of non-compensated Z-linked genes in somatic sex differentiation in birds. ..
  40. Deng X, Nguyen D, Hansen R, Van Dyke D, Gartler S, Disteche C. Dosage regulation of the active X chromosome in human triploid cells. PLoS Genet. 2009;5:e1000751 pubmed publisher
    ..Indeed, we found that there was a range of individual X-linked gene expression in relation to ploidy and that a small subset ( approximately 7%) of genes had expression levels apparently proportional to the number of autosomal sets. ..
  41. Lucchesi J. The structure-function link of compensated chromatin in Drosophila. Curr Opin Genet Dev. 2009;19:550-6 pubmed publisher
    ..Further progress in understanding the function of this complex will benefit from biophysical approaches. ..
  42. Bachtrog D, Jensen J, Zhang Z. Accelerated adaptive evolution on a newly formed X chromosome. PLoS Biol. 2009;7:e82 pubmed publisher
  43. Ho K, Deakin J, Wright M, Graves J, Grützner F. Replication asynchrony and differential condensation of X chromosomes in female platypus (Ornithorhynchus anatinus). Reprod Fertil Dev. 2009;21:952-63 pubmed publisher
    ..We discuss these results in relation to recent gene expression analysis of X-linked genes, which together give us insights into possible mechanisms of dosage compensation in platypus. ..
  44. Barbash D. Genetic testing of the hypothesis that hybrid male lethality results from a failure in dosage compensation. Genetics. 2010;184:313-6 pubmed publisher
    ..melanogaster X chromosome. Contrary to the predictions of this hypothesis, mutations in four essential D. melanogaster dosage compensation genes are shown here to moderately increase rather than decrease hybrid male viability...
  45. Prabhakaran M, Kelley R. A new strategy for isolating genes controlling dosage compensation in Drosophila using a simple epigenetic mosaic eye phenotype. BMC Biol. 2010;8:80 pubmed publisher
    ..This strategy is a promising alternative route for identifying previously unknown components of the dosage compensation pathway and novel alleles of known MSL proteins. ..
  46. McQueen H, Clinton M. Avian sex chromosomes: dosage compensation matters. Chromosome Res. 2009;17:687-97 pubmed publisher
    ..The implications of this new picture of avian dosage compensation for avian sex determination are discussed, along with a possible mechanism of avian dosage compensation. ..
  47. Csankovszki G, Petty E, Collette K. The worm solution: a chromosome-full of condensin helps gene expression go down. Chromosome Res. 2009;17:621-35 pubmed publisher
    ..Worm dosage compensation represents an excellent model system to study how condensin-mediated changes in higher order chromatin organization affect gene expression. ..
  48. Forsdyke D. X chromosome reactivation perturbs intracellular self/not-self discrimination. Immunol Cell Biol. 2009;87:525-8 pubmed publisher
  49. Carelle Calmels N, Saugier Veber P, Girard Lemaire F, Rudolf G, Doray B, Guerin E, et al. Genetic compensation in a human genomic disorder. N Engl J Med. 2009;360:1211-6 pubmed publisher
    ..This finding has implications for genetic counseling and represents a case of genetic compensation in a human genomic disorder. ..
  50. Fauth T, Müller Planitz F, König C, Straub T, Becker P. The DNA binding CXC domain of MSL2 is required for faithful targeting the Dosage Compensation Complex to the X chromosome. Nucleic Acids Res. 2010;38:3209-21 pubmed publisher
    ..Reporter gene assays and localization of GFP-fusion proteins confirm the important contribution of the CXC domain for DCC targeting in vivo. ..
  51. Kravets A, Qin H, Ahmad A, Bethlendy G, Gao Q, Rustchenko E. Widespread occurrence of dosage compensation in Candida albicans. PLoS ONE. 2010;5:e10856 pubmed publisher
    ..We suggest that C. albicans's unusual regulation of gene expression by the loss and gain of entire chromosomes is coupled with widespread compensation of gene dosage at the transcriptional level. ..
  52. Bondy C, Cheng C. Monosomy for the X chromosome. Chromosome Res. 2009;17:649-58 pubmed publisher
    ..This article reviews observations and arguments attempting to explain the phenotypic effects of X monosomy in humans and other mammals in terms of X chromosome gene dosage. ..
  53. Csankovszki G. Condensin function in dosage compensation. Epigenetics. 2009;4:212-5 pubmed
    ..We discuss how during worm dosage compensation a condensin-mediated function may guide the organization of the interphase chromatin fibers, leading to the formation of a repressive nuclear compartment. ..