Evolution of the androgen receptor: Perspectives from human health to dancing birds

Publication date: Available online 13 September 2019Source: Molecular and Cellular EndocrinologyAuthor(s): Eric R. Schuppe, Meredith C. Miles, Matthew J. FuxjagerAbstractAndrogenic hormones orchestrate the development and activation of diverse reproductive phenotypes across vertebrates. Although extensive work investigates how selection for these traits modifies individual elements of this signaling system (e.g., hormone or androgen receptor [AR] levels), we know less about natural variation in the AR sequence across vertebrates. Our knowledge of AR sequence mutations is largely limited to work in human patients or cell-lines, providing a framework to contextualize single mutations at the expense of evolutionary timescale. Here we unite both perspectives in a review that explores the functional significance of AR on a domain-by-domain basis, using existing knowledge to highlight how and why each region might evolve. We then examine AR sequence variation on different timescales by examining sequence variation in clades originating in the Cambrian (vertebrates;>500 mya) and Cretaceous (birds;>65 mya). In each case, we characterize how the receptor has changed over time and discuss which regions are most likely to evolve in response to selection. Overall, domains that are required for androgenic signaling to function (e.g., DNA- and ligand-binding) tend to be conserved. Meanwhile, areas that interface with co-regulatory molecules can exhibit notable variation even between closel...

Source: Molecular and Cellular Endocrinology - September 14, 2019 Category: Endocrinology Source Type: research