Oxygen deprivation produces symptoms such as fatigue, headaches, and confusion
that are collectively referred to as hypoxia. A vacation in the Rocky
Mountains of the US, where the partial pressure of oxygen is just 15% 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
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鈥攁 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 8000
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.
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