CAREER: Uncovering mechanisms that shape variation in how males and females differ in their gene expression

Auburn University, Auburn AL

Investigators

Abstract

Males and females often differ in appearance, as well as in less visible traits like how they respond to stress or how they age. These differences are largely explained by differences in how males and females express genes: how each sex uses the information in the genome to produce RNA and proteins. This type of difference in gene expression is thought to evolve as a result of genetic conflict - expression of a gene in the same way in both males and females could benefit one sex while having harmful effects in the other. Differences between males and females in gene expression can resolve such conflicts by allowing each to express a gene in a way that is beneficial for itself. In addition, differences in expression could even be fine-tuned to maximize the benefit according to the organism's environment. However, little is currently known about the molecular causes of differential gene expression between males and females, how it varies, and how it affects traits. This project focuses on differential expression in hormone signaling and looks at its genetic and environmental variation. It connects expression differences to reproductive traits and survivorship in typical and stressful environments. It will also test whether hormone signaling can resolve genetic conflict between the sexes. The project includes outreach and educational programs that will increase student awareness of and skills in research science in the areas of genomics, evolution and computational biology. A free summer science educational enrichment program for gifted students from underrepresented backgrounds in Alabama and Georgia will be run, supporting opportunities for these students and their teachers to engage in a summer research experiences at Auburn University. Also, work related to the project will be integrated into course-based undergraduate research experiences for Auburn University undergraduates. Recent work in the model organism Drosophila has shown that even under standardized conditions, the number and identity of genes that differ in expression between the sexes can vary substantially across genotypes. Similar changes are observed in response to environmental perturbations. These sex differences may also be modified by the nutrient and stress sensing insulin signaling pathway - one of three major, interconnected, hormone signaling pathways that regulate many fitness-related traits in adult insects. This project addresses challenges in understanding sex-differential expression and its evolution by focusing on a single type of conflict, intralocus conflict, and a single set of pathways that regulate sexually dimorphic traits, the insulin and ecdysone hormone signaling pathways. Genetic and environmental variability will be assessed and used to relate sex-differences in expression to sex-differences in fitness-related traits for individual alleles of sex-differentially expressed genes. Transcriptomic analyses of expression variation among outbred genotypes will be combined with molecular-genetic and environmental perturbations in a novel way. Allele-specific expression studies will be connected to allele-specific assays of fitness-related traits and combined with population genomic studies focused on the cis regulatory regions responsible for hormone regulation, as well as protein coding regions of hormone signaling regulated genes. While there is considerable diversity in sex determination mechanisms across taxa, the insulin-signaling pathway is widely conserved, as is steroid hormone signaling through nuclear receptor superfamily members. The knowledge that will be gained as a result of this project will therefore be broadly important for a mechanistic understanding of sexual conflict and the origins of sexual dimorphism, especially with respect to the role of environment. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.