Effects of Polymorphism in the Hypoxia Signaling Pathway on Oxygen Delivery and Mitochondrial Integrity
Open Access
- Author:
- Doerfler, William Reed
- Area of Honors:
- Biology
- Degree:
- Bachelor of Science
- Document Type:
- Thesis
- Thesis Supervisors:
- Dr. James Harold Marden, Thesis Supervisor
Tracy Lee Langkilde, Faculty Reader
Dr. James Harold Marden, Thesis Honors Advisor - Keywords:
- hypoxia signaling
Succinate dehydrogenase
mitochondrial integrity - Abstract:
- Oxygen delivery to tissues is of paramount evolutionary importance in aerobic organisms because it allows for the production of energy that can be used for fitness-related processes such as growth and reproduction. Insects deliver oxygen to tissues through tube-like networks of tracheae and tracheoles whose size and branching is increased during development by the action of the hypoxia inducible factor (HIF) pathway. A key transcription factor in the hypoxia inducible pathway is HIF 1-α, which is regulated by the substrate of the TCA cycle enzyme, succinate dehydrogenase (SDH). Previous work has shown that human loss-of-function mutations in the gene encoding succinate dehydrogenase subunit d, Sdhd, constitutively activate the hypoxia inducible pathway, and cause the development of vascularized tumors. Here we show that in lowland populations of Glanville fritillary butterflies (Melitaea cinxia) subtle allelic variation in the Sdhd gene which does not result in complete loss of SDH activity is associated with differences in tracheal abundance and mitochondrial integrity. Both of these traits are related to a molecular marker for the activation level of the hypoxia inducible pathway. These physiological traits presumably involve fitness tradeoffs, thus allowing the alleles to be maintained in populations over time. These results could also be applicable to other species, including humans, providing new insight into how organisms sense and respond to changes in oxygen, which in turn affects their development of important physiological traits.