The Y chromosome provides an unusual opportunity to examine population genetic processes like hitchhiking and background selection because of its recombinational isolation from other chromosomes, its effectively haploid transmission, and its restriction to males. Progress in studying Y chromosome population genetics of Drosophila has been held back by our ignorance of protein-coding genes and single-copy sequence. By using BLAST in the reverse of the normal approach, we have successfully identified eight new protein-coding genes on the Y chromosome of D. melanogaster. We are now in a position to provide a thorough quantification of patterns of variation on the Y chromosome of D. melanogaster, and to place this in the context of interspecific sequence divergence with related species. Four competing models, not all mutually exclusive, make predictions about levels of variation on a Y chromosome. They are Muller's ratchet, background selection, the Hill-Robertson effect, and hitchhiking. All four lead to the prediction that standing levels of variation on the Y ought to be depressed compared to autosomes, but they make different claims about the frequency spectrum, degree of population subdivision, and age distribution of alleles. We propose to parameterize and to quantitatively weigh the merits of these competing hypotheses through the following three aims: First, we will quantify and model intraspecific polymorphism in protein-coding genes on the Y chromosome of D. melanogaster by a combination of dHPLC and direct sequencing of Y-linked protein-coding genes in a set of 96 Y chromosome replacement lines of global distribution. Second, we will obtain corresponding sequences from a series of related species, in order to determine divergence rates and to characterize the molecular evolution of intronic Y heterochromatin. Finally, we will test associations between segregating Y variation and variation in sperm function through sperm kinematics assays and tests of sperm competitive ability. These studies will establish D. melanogaster as a key experimental system for analysis of Y chromosome polymorphism and molecular evolution.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM064590-03
Application #
6654883
Study Section
Genetics Study Section (GEN)
Program Officer
Eckstrand, Irene A
Project Start
2002-01-01
Project End
2005-12-31
Budget Start
2003-01-01
Budget End
2003-12-31
Support Year
3
Fiscal Year
2003
Total Cost
$192,697
Indirect Cost
Name
Cornell University
Department
Biochemistry
Type
Schools of Arts and Sciences
DUNS #
872612445
City
Ithaca
State
NY
Country
United States
Zip Code
14850
Unckless, Robert L; Clark, Andrew G; Messer, Philipp W (2017) Evolution of Resistance Against CRISPR/Cas9 Gene Drive. Genetics 205:827-841
Koerich, Leonardo B; Dupim, Eduardo G; Faria, Leonardo L et al. (2016) First report of Y-linked genes in the kissing bug Rhodnius prolixus. BMC Genomics 17:100
Carvalho, Antonio Bernardo; Vicoso, Beatriz; Russo, Claudia A M et al. (2015) Birth of a new gene on the Y chromosome of Drosophila melanogaster. Proc Natl Acad Sci U S A 112:12450-5
Meisel, Richard P; Scott, Jeffrey G; Clark, Andrew G (2015) Transcriptome Differences between Alternative Sex Determining Genotypes in the House Fly, Musca domestica. Genome Biol Evol 7:2051-61
Connallon, Tim; Clark, Andrew G (2015) The distribution of fitness effects in an uncertain world. Evolution 69:1610-1618
Krsticevic, Flavia J; Schrago, Carlos G; Carvalho, A Bernardo (2015) Long-Read Single Molecule Sequencing to Resolve Tandem Gene Copies: The Mst77Y Region on the Drosophila melanogaster Y Chromosome. G3 (Bethesda) 5:1145-50
Hoskins, Roger A; Carlson, Joseph W; Wan, Kenneth H et al. (2015) The Release 6 reference sequence of the Drosophila melanogaster genome. Genome Res 25:445-58
Wang, Xu; Werren, John H; Clark, Andrew G (2015) Genetic and epigenetic architecture of sex-biased expression in the jewel wasps Nasonia vitripennis and giraulti. Proc Natl Acad Sci U S A 112:E3545-54
Unckless, Robert L; Messer, Philipp W; Connallon, Tim et al. (2015) Modeling the Manipulation of Natural Populations by the Mutagenic Chain Reaction. Genetics 201:425-31
Unckless, Robert L; Larracuente, Amanda M; Clark, Andrew G (2015) Sex-ratio meiotic drive and Y-linked resistance in Drosophila affinis. Genetics 199:831-40

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