Polyploidization, gene dosage, and the evolution of hormonal phenotypes

Steroid hormones (adrenal glucocorticoids and gonadal steroids) have been extensively studied in the context of ecology and behavior because of the integral roles these hormones play in mediating phenotypic changes that are crucial for survival and reproduction. One of the most striking findings emerging from such studies is the diversity that exists with respect to regulation of these hormones. For example, circulating levels of these hormones and the extent to which elevated glucocorticoids suppress the production of gonadal steroids are both highly variable across vertebrate species. This study examines adrenal glucocorticoids and gonadal steroids in a diploid-polyploid treefrog species complex to understand how polyploidization (duplication of the genome) contributes to this variation. Polyploidization is expected to drive modifications in hormonal regulation because associated changes in gene copy number can introduce novel gene expression patterns and/or increase rates of mutation that alter the expression of gene products governing hormone levels and hormonal interactions. The proposed study is relevant to understanding broad patterns of variation in hormonal regulation because polyploidy is a historical feature of vertebrates and a major source of variation in gene copy number in living vertebrates. This research will be integrated with summer research programs at the sponsoring institution to recruit at least eight high-school students from groups underserved in STEM fields to participate in the project. The project also involves training of undergraduate and graduate students and one post-doctoral associate, who will work closely with one another, high- school students, and the principal investigators, to cross-foster training and career development through peer mentoring.

Circulating levels of adrenal glucocorticoids and gonadal steroids, and interactions between these hormones, are remarkably variable across vertebrates, but the genetic underpinnings giving rise to this diversity are poorly understood. This study examines endocrine regulation in polyploids to understand how associated changes in gene copy number (i.e., gene dosage) contribute to this extraordinary diversity. Polyploidization and associated changes in gene dosage can dramatically influence the evolution of the phenotype by altering gene expression patterns and/or by increasing gene mutation rates, but how polyploidization contributes to modifications in hormonal regulation remains largely unstudied. The proposed work examines regulation of adrenal glucocorticoids and gonadal steroids in three natural tetraploid gray treefrog lineages and their diploid ancestor to understand how polyploidization impacts endocrine control. By characterizing hormone levels and interactions between the hypothalamic-pituitary-adrenal/interrenal and hypothalamic-pituitary-gonadal axes, comparing steroid receptor and binding protein mRNA expression levels and sequences, and examining steroid binding protein levels and kinetics in diploid and tetraploid treefrogs, this study will elucidate how changes in gene dosage through polyploidization impact hormonal regulation. The broader impacts of this research include diverse student involvement in field and lab-based interdisciplinary research in endocrinology, genetics, and neuroscience. Rural high-school students will be recruited to participate in the research during summers and the impact of their experiences will be assessed.

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.