The Y chromosome has long been known to play a critical role in male fertility;however, it has been thought to play relatively little role in organismal fitness or health more broadly. The recent observation that hundreds to thousands of genes differ in expression between Drosophila melanogaster lines that differ only at the Y chromosome suggests that Y-linked regulatory variation (YRV), likely attributable to differences in repetitive, heterochromatin-binding sequences on the Y chromosome, is important and widespread. This proposal seeks to answer two fundamental questions about this novel phenomenon. First, to what extent does the divergence of Y chromosomes between species contribute to divergent gene expression (a likely source of many phenotypic differences between species)? Second, how does YRV affect our understanding of how Y chromosomes evolve (of considerable importance for understanding the evolutionary degeneration of sex chromosomes) and of how gene expression differences between species evolve? In order to answer these questions, a combined experimental and theoretical approach will be employed. Using existing Drosophila stocks of species closely related to D. melanogaster, Y chromosomes from D. sechellia will be introgressed into D. simulans. By comparing gene expression using custom-designed species-specific microarrays between lines with native D. simulans Y chromosomes and introgression lines that carry a D. sechellia Y chromosome but are otherwise genetically identical, it will be possible to identify genes that are differentially expressed due solely to divergence of the Y chromosome between this two species. Using low-cost spotted cDNA microarrays that target the differentially expressed genes identified in this initial survey, subsequent experiments will compare different D. sechellia Y chromosomes in both a D. sechellia genomic background and a D. simulans background to estimate polymorphism and divergence in gene expression, crucial parameters for evolutionary modeling. Using these data, and combined with revised models Y chromosome evolution that incorporate the unique features of YRV, models of gene expression divergence will allow inference about the evolutionary forces that have governed the divergence of Y-linked gene expression between species. The work proposed here uses a Drosophila model system to disentangle the effects of the Y chromosome from other chromosomes on organismal phenotypes. Understanding how differences among Y chromosomes affect organismal phenotype is a critical first step towards understanding the potential role of the Y chromosome in human health and disease.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32GM086950-03
Application #
8005042
Study Section
Special Emphasis Panel (ZRG1-GGG-G (21))
Program Officer
Carter, Anthony D
Project Start
2009-01-01
Project End
2011-12-31
Budget Start
2011-01-01
Budget End
2011-12-31
Support Year
3
Fiscal Year
2011
Total Cost
$51,326
Indirect Cost
Name
Harvard University
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
082359691
City
Cambridge
State
MA
Country
United States
Zip Code
02138
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Sackton, Timothy B; Montenegro, Horacio; Hartl, Daniel L et al. (2011) Interspecific Y chromosome introgressions disrupt testis-specific gene expression and male reproductive phenotypes in Drosophila. Proc Natl Acad Sci U S A 108:17046-51