The main goal of this project is to perform a comparative genomics study of genes encoding mammalian seminal fluid proteins. Proteins found in seminal fluid accompanying sperm show drastic effects on reproduction, such as manipulating female behavior. Even in mammals they participate in competition between sperm of different males, and serve to protect sperm from infection by pathogens. These types of roles require the proteins to constantly adapt to stay ahead of the competition. Such adaptive pressures on proteins leave characteristic signatures in the DNA sequences that encode them. We will use these signatures to identify adaptive evolution in rodent seminal proteins and compare patterns to those previously found in primates. Additionally, we will investigate the origin of seminal fluid genes in primates and rodents - are the same orthologous genes used between these groups? ? ? This proposal is aimed at the identification of genes encoding mouse seminal fluid proteins and the comparative genomics of mouse and human seminal fluid genes. Seminal fluid is likely to regulate many aspects of fertilization. Factors in the seminal fluid could be important for sperm maturation, modulating female immune response to protect sperm, sperm storage, and even sperm - egg interaction. Thus, it is important to characterize the components of mammalian seminal fluid. Evolutionary dynamics of these genes could also be important for cancer research. It is important to explore the possibility that adaptive evolution of seminal fluid factors contributes to disease through pleiotropic effects. Adaptation in prostate-expressed genes may benefit primates during their reproductive lifespan, but could lead to damaging side effects in later life. ? ? ?

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Small Research Grants (R03)
Project #
1R03HD054631-01A1
Application #
7313525
Study Section
Pediatrics Subcommittee (CHHD)
Program Officer
Rankin, Tracy L
Project Start
2007-08-15
Project End
2009-07-31
Budget Start
2007-08-15
Budget End
2008-07-31
Support Year
1
Fiscal Year
2007
Total Cost
$78,000
Indirect Cost
Name
University of Washington
Department
Genetics
Type
Schools of Medicine
DUNS #
605799469
City
Seattle
State
WA
Country
United States
Zip Code
98195
Vacquier, Victor D; Swanson, Willie J (2011) Selection in the rapid evolution of gamete recognition proteins in marine invertebrates. Cold Spring Harb Perspect Biol 3:a002931
Swanson, Willie J; Aagaard, Jan E; Vacquier, Victor D et al. (2011) The molecular basis of sex: linking yeast to human. Mol Biol Evol 28:1963-6
Aagaard, Jan E; Vacquier, Victor D; MacCoss, Michael J et al. (2010) ZP domain proteins in the abalone egg coat include a paralog of VERL under positive selection that binds lysin and 18-kDa sperm proteins. Mol Biol Evol 27:193-203
Findlay, Geoffrey D; MacCoss, Michael J; Swanson, Willie J (2009) Proteomic discovery of previously unannotated, rapidly evolving seminal fluid genes in Drosophila. Genome Res 19:886-96
Kelley, Joanna L; Turkheimer, Kayley; Haney, Margo et al. (2009) Targeted resequencing of two genes, RAGE and POLL, confirms findings from a genome-wide scan for adaptive evolution and provides evidence for positive selection in additional populations. Hum Mol Genet 18:779-84
Karn, Robert C; Clark, Nathaniel L; Nguyen, Eric D et al. (2008) Adaptive evolution in rodent seminal vesicle secretion proteins. Mol Biol Evol 25:2301-10
Kelley, Joanna L; Swanson, Willie J (2008) Positive selection in the human genome: from genome scans to biological significance. Annu Rev Genomics Hum Genet 9:143-60
Kelley, Joanna L; Swanson, Willie J (2008) Dietary change and adaptive evolution of enamelin in humans and among primates. Genetics 178:1595-603
Findlay, Geoffrey D; Yi, Xianhua; Maccoss, Michael J et al. (2008) Proteomics reveals novel Drosophila seminal fluid proteins transferred at mating. PLoS Biol 6:e178