Oxygen deprivation produces symptoms such as fatigue, headaches, and confusion that are collectively referred to as hypoxia. A vacation in the Rocky Mountains in the United States, where the partial pressure of oxygen is just 15 percent lower than you are accustomed to on the coast, can induce these symptoms. The body has a very narrow range of environment oxygen tolerance. It essentially has no capacity for storage of oxygen that is continuously consumed to maintain energy homeostasis.
The response to oxygen deprivation is to increase breathing rate and increase the volume of each breath. The input for a negative-feedback loop that maintains homeostasis by detecting oxygen concentrations is a sensor (the carotid body) located on the interior of the carotid artery. The output is at the diaphragm. The signal is processed in the respiratory centers (RCs) of the medulla in the brainstem.

 

A. Describe how the nervous system integrates information about oxygen concentration in the blood to maintain homeostasis. In your description, include the concepts of negative feedback and a set point. An alternative model (Evens et al., Biochemical Journal, 473, 2016) of the response to oxygen deprivation is suggested by the observation that high-altitude Andean populations have a gene for a protein kinase (AMPK encoded by PRKAA1) that has a fixed single nucleotide variation. This AMP-activated kinase is coupled with mitochondrial oxidative phosphorylation to detect reduced oxygen and signal the RCs of the medulla directly—a distributed network for detection and response. The authors of this work note that a homologous gene in yeast allows colony-wide signaling to switch individuals in the colony from glycolysis to oxidative phosphorylation in response to changes in glucose resources.

 

B. Describe the connection of a changing environment to changing genomes in both species in terms of the adaptive advantage provided and the likelihood that an AMPK signaling process has been conserved across domains. Studies of a genetic adaptation in Tibetan population have shown that other mutations have been selected. One mutation EPAS1 was shown to be correlated with increased lactic acid concentrations in the blood. Another mutation, PPARA, was found to be correlated with fatty acid production, which is typically seen during hibernation (Ge et al., Molecular Genetics and Metabolism, 106, 2012; Lorenzo et al., Nature Genetics, 46, 2014).

 

C. Analyze these observations in terms of the regulation of metabolism due to changes in genetic makeup and construct an explanation for the divergence of the homeostatic mechanisms as an adaptation to the environment. The Tibetan population is not isolated. However, these investigations show the near dominance of the mutated form of these two genes has arisen in just 8,000 years. Neanderthal, Denisovans, and ancestors of modern humans were contemporaries.

 

D. Describe conditions that lead to speciation in terms of the accumulation of many small genetic changes where very sharp differences in oxygen availability were geographically imposed.