Because the Y chromosome is present in just one copy and only in males, it faces a diminished capacity to purge deleterious mutations. Our understanding of the complete set of functional elements on the Y chromosome lags far behind the rest of the genome, and this is especially true for the Drosophila model system. There are now 12 complete genome sequences for species of Drosophila whose well-known phylogeny provides a rich resource for analysis of Y chromosome dynamics. A major recent finding is that among these 12 species the gene gains largely outnumber gene losses, which is at odds with the view that the Y is simply degenerating. In this proposal, we aim first, to complete the annotation of Y-linked genes across the Drosophila species whose genomes have been sequenced. We have devised and perfected a highly efficient Illumina/Solexa-sequence based method for identifying Y-specific contigs, and plan to use it to identify, assemble, and annotate the Y-linked contigs and their embedded genes. RNAi knock-down will be used to identify the genes on the D. melanogaster and D. pseudoobscura Y that are essential for male fertility. Second, we will quantify and model intraspecific polymorphism in protein- coding genes on the Y chromosome of D. melanogaster, D. simulans, and D. pseudoobscura, as well as interspecific divergence among the 12 species. Analysis of polymorphism and divergence has started to place bounds on the levels of background selection acting on Drosophila Y chromosomes. The roles of Muller's ratchet, hitchhiking by selective sweeps, and the Hill-Robertson effect will also be assessed by fitting models of sequence evolution to site frequency data using approximate Bayesian computation. D. simulans is included as a second and more polymorphic cosmopolitan species to compare to melanogaster, and D. pseudoobscura's Y chromosome is derived within the past 18 Myr from formerly autosomal sequences. Third, we will assemble and finish the Y-to-autosome translocated region of D. pseudoobscura genome. This is motivated by the translocation of heterochromatic, Y-linked genes onto the dot chromosome in this species, presenting a fortuitous opportunity to study the effect of the loss of male-restricted transmission and the loss of heterochromatin in this region. This project will entail BAC sequencing, RT-PCR tests of expression, and analysis of polymorphism in this region. Finally, the fourth aim is to characterize and quantify functional variation associated with the Y chromosome. Simple population genetic models predict rapid fixation of favored Y chromosomal alleles, and yet there is compelling evidence that functional polymorphism is maintained. Theory further shows that interactions between Y and other chromosomes are more likely to be able to retain polymorphism, and recent work has demonstrated large effects of Y-linked variation on gene expression throughout the genome. Experiments designed specifically to quantify the role of epistasis in Y chromosomal evolution are well motivated.

Public Health Relevance

The Y chromosome of Drosophila provides an ideal system for testing many concepts related to the evolution of sex chromosomes. The proposed study entails primary discovery of most of the Y- linked genes across a group of 12 species and a detailed study of their evolutionary divergence.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM064590-09
Application #
8324312
Study Section
Genetic Variation and Evolution Study Section (GVE)
Program Officer
Eckstrand, Irene A
Project Start
2002-01-01
Project End
2014-08-31
Budget Start
2012-09-01
Budget End
2014-08-31
Support Year
9
Fiscal Year
2012
Total Cost
$292,043
Indirect Cost
$80,129
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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