Dosage compensation is the process by which the expression of X-linked genes is altered in one sex to counterbalance the difference in X-chromosome and autosome number in the heterogametic sex. Degeneration of the non-recombining Y chromosome is a general facet of sex chromosome evolution. Selective pressure to equalize expression levels of X- linked genes in males accompanies Y-chromosome degeneration, thus driving the evolution of dosage compensation. Drosophila miranda - a species for which we recently generated a de novo genome sequence assembly - has three sex chromosomes of different age and at different stages of transition from ordinary autosomes into heteromorphic sex chromosomes. Specifically, X-L is the ancestral sex chromosome of the genus Drosophila and >60MY old, X-R is shared by members of the D. pseudoobscura subgroup and >10MY old, while its neo-sex chromosome (about 1MY old) still largely resembles an autosome, but the neo-X is evolving partial dosage compensation. D. miranda therefore provides a unique system to study the evolution of dosage compensation in action using a comparative and functional genomics approach. We will use ChIP-seq techniques together with whole-genome population analysis to functionally characterize the targeting of the dosage compensation complex to the X chromosome, and how it evolves.

Public Health Relevance

Expression networks are often fine-tuned, and chromosomal aneuploidy and changes in gene dosage can disturb the overall balance of gene expression networks, and are associated with several known human diseases and birth defects (Down syndrome results from an extra copy of Chromosome 21), and chromosomal aneuploidies are also frequent in cancer cells. Sex chromosomes, in contrast, provide systems of naturally occurring aneuploidy, with females having two X chromosomes and males having one X and a Y, resulting in X monosomy in males, and unique gene regulation strategies have evolved to compensate for this gene-dose deficiency in males. We will use the model species Drosophila to investigate evolutionary and functional aspects of dosage compensation, which will help to understand the effects of aneuploidy on gene expression and the mechanisms that alleviate aneuploidy-induced expression imbalances of the genome.

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
Research Project (R01)
Project #
Application #
Study Section
Genetic Variation and Evolution Study Section (GVE)
Program Officer
Eckstrand, Irene A
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of California Berkeley
Schools of Arts and Sciences
United States
Zip Code
Wong Miller, Karen M; Bracewell, Ryan R; Eisen, Michael B et al. (2017) Patterns of Genome-Wide Diversity and Population Structure in the Drosophila athabasca Species Complex. Mol Biol Evol 34:1912-1923
Mahajan, Shivani; Bachtrog, Doris (2017) Convergent evolution of Y chromosome gene content in flies. Nat Commun 8:785
Blackmon, Heath; Ross, Laura; Bachtrog, Doris (2017) Sex Determination, Sex Chromosomes, and Karyotype Evolution in Insects. J Hered 108:78-93
Gibilisco, Lauren; Zhou, Qi; Mahajan, Shivani et al. (2016) Alternative Splicing within and between Drosophila Species, Sexes, Tissues, and Developmental Stages. PLoS Genet 12:e1006464
Zhou, Qi; Bachtrog, Doris (2015) Ancestral Chromatin Configuration Constrains Chromatin Evolution on Differentiating Sex Chromosomes in Drosophila. PLoS Genet 11:e1005331
Ellison, Christopher E; Bachtrog, Doris (2015) Non-allelic gene conversion enables rapid evolutionary change at multiple regulatory sites encoded by transposable elements. Elife 4:
Mahajan, Shivani; Bachtrog, Doris (2015) Partial dosage compensation in Strepsiptera, a sister group of beetles. Genome Biol Evol 7:591-600
Vicoso, Beatriz; Bachtrog, Doris (2015) Numerous transitions of sex chromosomes in Diptera. PLoS Biol 13:e1002078
Assis, Raquel; Bachtrog, Doris (2015) Rapid divergence and diversification of mammalian duplicate gene functions. BMC Evol Biol 15:138
Brown, Emily J; Bachtrog, Doris (2014) The chromatin landscape of Drosophila: comparisons between species, sexes, and chromosomes. Genome Res 24:1125-37

Showing the most recent 10 out of 51 publications