Successful reproduction in all vertebrates depends upon the action of gonadotropin-releasing hormone (GnRH). Because GnRH is present in diverse animals ranging from mammals to tunicates, it is hypothesized that GnRH may have already been present 630 million years ago in an ancestor that gave rise to vertebrates and invertebrates. If proven, GnRH could be one of the most ancient hormones to persist through evolution. As such, its evolutionary pattern could reveal much about how an important hormone changed its function and structure over time. Dr. Tsai's recent data that a GnRH-like molecule is present in the sea slug, Aplysia californica, proved that GnRH arose very early during evolution. This project utilizes a combination of molecular, cellular and whole organism approaches to characterize the receptor for Aplysia GnRH (ap-GnRH) and to understand what ap-GnRH does in the sea slug. This project will also allow Dr. Tsai to train graduate and undergraduate students interested in hormone evolution and strengthen collaborative ties with other trainees in the Ecology and Evolutionary Biology Department. In sum, this project will contribute substantially to our understanding of how evolutionary selection pressures drive changes in hormone structures and functions, and how these changes allow the organism to adapt better to the environment.
Gonadotropin-releasing hormone (GnRH) is a hormone critical for reproductive stimulation in all vertebrates. There is increasing evidence suggesting that GnRH is one of the most ancient hormones to persist through evolution. One key question was whether GnRH had always been a reproductive activator, or was once a general "all-purpose" hormone that was adopted for different functions in different organisms. Dr. Tsai’s investigation using a sea slug model suggests that GnRH in this animal is actually a regulator of feeding, movement, and general neural function, but not reproduction. This discovery represented a conceptual shift from the older belief that the ancient function of GnRH was reproductive, and that this function was retained in all animals possessing GnRH. The main intellectual merit of this work is the clarification of how a molecule evolved structurally and functionally over time, a process that is extremely difficult to study. Evolution is not a linear process. Traits are often lost and then re-acquired under different conditions. Since scientists cannot go back in time to study this process, they need to rely on a series of snapshots offered by animals at key evolutionary branch points to construct a model on how and when changes had occurred. Our work using the sea slug suggests that GnRH may have adopted a novel and key role in reproduction only recently in an ancestor to modern vertebrates. The overall implication is that many important and ancient hormones in vertebrates may have achieved their specialized roles in a similar fashion. Over the last 4 years, this work has supported the training of 4 undergraduate students, 2 postdoctoral fellows, and 2 graduate students. Further, this work supported the collaboration between Dr. Tsai and colleagues in the field of evolutionary biology to enhance the understanding of how hormones evolved functionally and structurally over time.