Open Access Highly Accessed Research article

Global analysis of X-chromosome dosage compensation

Vaijayanti Gupta1*, Michael Parisi1, David Sturgill1, Rachel Nuttall24, Michael Doctolero24, Olga K Dudko3, James D Malley3, P Scott Eastman24 and Brian Oliver1*

Author Affiliations

1 Laboratory of Cellular and Developmental Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, 50 South Drive, Bethesda, MD 20892, USA

2 Incyte Genomics, Palo Alto, CA 94304, USA

3 Mathematical and Statistical Computing Laboratory, Division of Computational Bioscience, Center for Information Technology, National Institutes of Health, Bethesda, MD 20982, USA

4 Current address: Quantum Dot Corporation, Hayward, CA 94545, USA

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Journal of Biology 2006, 5:3  doi:10.1186/jbiol30

Published: 16 February 2006

Abstract

Background

Drosophila melanogaster females have two X chromosomes and two autosome sets (XX;AA), while males have a single X chromosome and two autosome sets (X;AA). Drosophila male somatic cells compensate for a single copy of the X chromosome by deploying male-specific-lethal (MSL) complexes that increase transcription from the X chromosome. Male germ cells lack MSL complexes, indicating that either germline X-chromosome dosage compensation is MSL-independent, or that germ cells do not carry out dosage compensation.

Results

To investigate whether dosage compensation occurs in germ cells, we directly assayed X-chromosome transcripts using DNA microarrays and show equivalent expression in XX;AA and X;AA germline tissues. In X;AA germ cells, expression from the single X chromosome is about twice that of a single autosome. This mechanism ensures balanced X-chromosome expression between the sexes and, more importantly, it ensures balanced expression between the single X chromosome and the autosome set. Oddly, the inactivation of an X chromosome in mammalian females reduces the effective X-chromosome dose and means that females face the same X-chromosome transcript deficiency as males. Contrary to most current dosage-compensation models, we also show increased X-chromosome expression in X;AA and XX;AA somatic cells of Caenorhabditis elegans and mice.

Conclusion

Drosophila germ cells compensate for X-chromosome dose. This occurs by equilibrating X-chromosome and autosome expression in X;AA cells. Increased expression of the X chromosome in X;AA individuals appears to be phylogenetically conserved.