Males and females differ profoundly at virtually all levels of biological organization, from morphology and behavior to gene expression and disease risk. A key force that molds these differences is sexually antagonistic selection, in which a gene that is beneficial in one sex is detrimental in the other. This type of selection is thought to drive the evolution of several features of the genome, and it has also been hypothesized to underlie sex-specific differences in disease susceptibility in humans. Despite its importance, we have little direct information about where sexually antagonistic selection acts in the genome or about its role in creating differences between the sexes. Sex chromosomes are the most promising context in which to study sexually antagonistic selection because they are predicted to be hotspots for the accumulation of genes experiencing this type of selection. Furthermore, sexually antagonistic selection is thought to be responsible for the evolution of the distinctive properties of sex chromosomes, such as a reduction in recombination between the X and the Y, and the subsequent degeneration of the Y. Much of the existing data from sex chromosomes, however, comes from systems with sex chromosomes that are highly degenerate and gene-poor, rendering the identification of genes experiencing sexually antagonistic selection difficult or impossible. Stickleback fishes are an emerging model system whose sex chromosomes still recombine and are gene-rich, making them ideally suited for studying sexually antagonistic selection. This research project will exploit those properties to learn how sexually antagonistic selection sculpts chromosomes, genes, and phenotypes. The three major aims will: (1) use genetic, cytogenetic, and genomic tools to reveal how recombination between the X and Y chromosomes becomes suppressed; (2) obtain whole genome sequences to study how the many differences between males and females alter the evolutionary trajectories of genes and chromosomes; and (3) use new statistical methods to identify the genetic and phenotypic targets of sexually antagonistic selection. The results from this project will be useful in context far beyond sex chromosomes in sticklebacks. It will generate technical innovations, such as new statistical methods for analyzing DNA variation that will be valuable for studies of chromosomal rearrangements on autosomes in diverse taxa. Furthermore, insights from this work will provide perspectives on the potential for selection to establish genes that are detrimental to health in al species, including humans.

Public Health Relevance

Males and females differ in virtually all respects, including in their risk for common diseases. However, the genes underlying these differences and the ways they become established are mostly unknown. This project exploits the young and gene-rich sex chromosomes of stickleback fish to reveal how evolution establishes genes that have conflicting effects on the health of males and females, and to learn how this changes the very structure of the genome.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
1R01GM116853-01
Application #
9003570
Study Section
Genetic Variation and Evolution Study Section (GVE)
Program Officer
Janes, Daniel E
Project Start
2015-09-17
Project End
2019-05-31
Budget Start
2015-09-17
Budget End
2016-05-31
Support Year
1
Fiscal Year
2015
Total Cost
$571,012
Indirect Cost
$166,281
Name
Fred Hutchinson Cancer Research Center
Department
Type
DUNS #
078200995
City
Seattle
State
WA
Country
United States
Zip Code
98109
Peichel, Catherine L; Marques, David A (2017) The genetic and molecular architecture of phenotypic diversity in sticklebacks. Philos Trans R Soc Lond B Biol Sci 372:
Fontaine, Albin; Filipovic, Igor; Fansiri, Thanyalak et al. (2017) Extensive Genetic Differentiation between Homomorphic Sex Chromosomes in the Mosquito Vector, Aedes aegypti. Genome Biol Evol 9:2322-2335
Kirkpatrick, Mark (2017) The Evolution of Genome Structure by Natural and Sexual Selection. J Hered 108:3-11
Peichel, Catherine L; Sullivan, Shawn T; Liachko, Ivan et al. (2017) Improvement of the Threespine Stickleback Genome Using a Hi-C-Based Proximity-Guided Assembly. J Hered 108:693-700
Peichel, Catherine L (2017) Chromosome Evolution: Molecular Mechanisms and Evolutionary Consequences. J Hered 108:1-2
Peichel, Catherine L (2017) Convergence and divergence in sex-chromosome evolution. Nat Genet 49:321-322
Cech, Jennifer N; Peichel, Catherine L (2016) Centromere inactivation on a neo-Y fusion chromosome in threespine stickleback fish. Chromosome Res 24:437-450
Cheng, Changde; Kirkpatrick, Mark (2016) Sex-Specific Selection and Sex-Biased Gene Expression in Humans and Flies. PLoS Genet 12:e1006170