Enter the text here that is the new abstract information for your application. This section must be no longer than 30 lines of text. Comparative genomics of sex chromosomes in Diptera: gene trafficking, dosage compensation, sex-biased expression and gene content evolution. Sex chromosomes are derived from ordinary autosomes but harbor many unique characteristics, including a nonrandom gene content, or sex-specific expression patterns. However, most of our knowledge of sex chromosome biology is restricted to a few model species, including humans or Drosophila, since identification of sex-linked genes traditionally requires laborious segregation analysis or physical mapping. Research in these two groups has revealed that sex chromosomes often show unusual, yet sometimes highly discordant patterns of genome evolution and function. In particular, X chromosomes of mammals show an excess of male genes, yet a deficiency in Drosophila;the X is dosage compensated through X inactivation in female mammals, yet is hyper-transcribed in Drosophila males;the gene content is highly conserved on the Y chromosome in primates and many Y genes have homologs on the X, yet turns over rapidly in Drosophila with no remaining X-Y homology. Thus, to disentangle species-specific patterns from general features of sex chromosomes, it is necessary to compare the genomic properties of several independently formed sex chromosomes. We have developed a new powerful statistical method for identifying a large number of sex-linked genes that is applicable to virtually any organism using next-generation sequencing techniques. This will allow us to examine sex chromosomes in several non-model organisms, and study the functional and evolutionary properties of sex chromosomes in an unprecedented way. We propose to use broad phylogenetic sampling in Diptera and novel sequencing-based methods to identify sex-linked sequences, combined with transcriptome profiling across sexes and tissues, and investigation of the sex-specific chromatin structure. This rich data set will allow us to identify transitions among sex chromosomes and sex determining mechanisms, and will reveal key principals that shape the evolution and function of independently evolved sex chromosomes in flies, including identification of the general mechanisms of dosage compensation and the evolution of sex-biased expression patterns.

Public Health Relevance

Evidence for the importance of genetic factors in male fertility is accumulating, and is often associated with genes that are expressed in testis. Comparative genome analysis has shown that testis genes show rapid turnover between species (that is, many novel genes unique to humans show testis-specific expression) and often avoid linkage to sex chromosomes. We will use model fly species to investigate the underlying causes for the rapid evolution of testis genes and their biased distribution in the genome, which will help to understand male infertility associated with defects in testis genes.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
2R01GM093182-05
Application #
8698035
Study Section
Genetic Variation and Evolution Study Section (GVE)
Program Officer
Janes, Daniel E
Project Start
2010-03-01
Project End
2018-06-30
Budget Start
2014-08-01
Budget End
2015-06-30
Support Year
5
Fiscal Year
2014
Total Cost
Indirect Cost
Name
University of California Berkeley
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
City
Berkeley
State
CA
Country
United States
Zip Code
94704
Assis, Raquel; Bachtrog, Doris (2015) Rapid divergence and diversification of mammalian duplicate gene functions. BMC Evol Biol 15:138
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
Bachtrog, Doris (2014) Signs of genomic battles in mouse sex chromosomes. Cell 159:716-8
Lott, Susan E; Villalta, Jacqueline E; Zhou, Qi et al. (2014) Sex-specific embryonic gene expression in species with newly evolved sex chromosomes. PLoS Genet 10:e1004159
Boussau, Bastien; Walton, Zaak; Delgado, Juan A et al. (2014) Strepsiptera, phylogenomics and the long branch attraction problem. PLoS One 9:e107709
Zhou, Qi; Zhang, Jilin; Bachtrog, Doris et al. (2014) Complex evolutionary trajectories of sex chromosomes across bird taxa. Science 346:1246338
Kaiser, Vera B; Bachtrog, Doris (2014) De novo transcriptome assembly reveals sex-specific selection acting on evolving neo-sex chromosomes in Drosophila miranda. BMC Genomics 15:241

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