Cambrian Explosion: oxygen and stem cell theory (Introduction)

by David Turell , Friday, March 09, 2018, 20:54 (2451 days ago) @ David Turell

This new theory uses the new abundance of oxygen and protected stem cells to allow the Cambrian explosion. Oxygen is dangerous unless controlled:

https://www.quantamagazine.org/oxygen-and-stem-cells-reshaped-animals-during-the-cambri...

"It is by no means certain that a big uptick in atmospheric oxygen caused the Cambrian explosion: Many scientists give more weight to alternative theories about the emergence of new genetic capabilities or major shifts in ecological interactions that prompted new forms to evolve. Nevertheless, animals in that period would have needed to develop physiological innovations to deal with the abundance of oxygen.

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"Their hypothesis is that the evolution of the capacity to maintain undifferentiated cells — even when those cells were exposed to higher levels of oxygen — allowed animals to keep stocks of stem cells for tissue growth and repair. That capacity, in turn, made it possible for animals to become more complex and diversify.

"Stem cells have a “pluripotent” ability to give rise to the other cell types that make up healthy tissues. Throughout life, they play a crucial part in the regeneration and repair of tissues. Scientists are still trying to find out what enables stem cells to maintain their pluripotent, undifferentiated state when other cells cannot.

"One factor researchers have identified is oxygen: The cells require low oxygen levels to remain in their stem states. Experiments have illustrated that exposing stem cells to greater amounts of oxygen usually causes them to differentiate abruptly. This observation explains why stem cells are so often sequestered in regions of the body like the bone marrow, where oxygen levels are relatively low (hypoxic).

"Påhlman and Hammarlund figured that if they could determine how our bodies and malignancies preserve those stem cells despite the oxygen, they might be able to explain how early animals solved their own oxygen problems millions of years ago.

"So they focused on a family of proteins called hypoxia-inducible factors (HIFs), chief among them the protein HIF-2α. Its activity is heavily implicated in cancers of the kidneys and the sympathetic nervous system (including the neuroblastomas that Påhlman studies).

"The HIFs help modulate how cells react to different oxygen conditions. When oxygen is low, cells activate HIFs to shift their metabolisms from aerobic to anaerobic and to start other processes that keep the cells alive; when oxygen is high, the HIFs are no longer needed and get degraded.

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"Hammarlund and Påhlman then took a leap: They posited that HIF-2α functions similarly in normal animal tissues. They’ve seen some preliminary evidence of this in the skin and the sympathetic nervous system (knocking out the protein in the latter interferes with its development), but further experiments are needed to confirm the idea.

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"Hammarlund then considered HIF-1α, the molecule in vertebrates that she and Påhlman describe as resembling “the ancestral HIF form” that would have evolved first. It behaves as a metabolic switch that allows cells to “enter or exit a low-oxygen consumption mode,” she said, so it would have allowed emerging animals to be less sensitive to oxygen fluctuations in their environments.

“'Organisms could start to manage stem cells better,” Hammarlund explained. Their tissues could grow with fewer oxygen-imposed constraints, so they could be made of more diverse cells growing in more varied structures. Moreover, the animals could begin to populate more habitats with varying oxygen levels. Hammarlund says that other researchers are exploring whether this is why the Ediacaran creatures, which disappeared at the start of the Cambrian and did not have this ability, lived in such deep parts of the ocean, where oxygen concentrations were more stable.

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"In short, the development of the HIF proteins presented the “proper key to get at the gold mine,” Hammarlund said. It wasn’t until HIF and HIF-2α came along that animals could start to use oxygen for more metabolic energy, build more elaborate tissues and cope better with oxygen damage. “The HIFs probably weren’t the only key, but they’re one we now know,” she said.

"She and Påhlman hope to uncover other mechanisms as well, but first they need to test essential components of their HIF hypothesis, primarily the idea that the hypoxia reaction is specifically invoked in normal tissues to maintain stem cells.

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"For now, Hammarlund and Påhlman’s ideas need to be substantiated by experimental evidence. And to tie them to broader mysteries about the Cambrian explosion, researchers would need to determine whether changes in atmospheric oxygen drove the development of the HIFs, and if so, to what extent. It’s a nuanced relationship, to be sure."

Comment: Oxygen is very toxic and must be controlled. This complex theory requires a designer running the show.