Cambrian 'Explosion' - "Hypoxia-Inducible Factors" & Surviving Oxygen Surplus


(George Brooks) #1

Scientists are on the verge of answering the age old question of why speciation went into over-drive during the Cambrian Epoch!:

It turns out that the genetic processes that allow DNA to remain relatively dormant (or in other words, “un-triggered” into any of hundreds of possible and quite specific outcomes) do not do well in a highly oxygenated environment. So as single celled life, like algae, started to produce an increasingly oxygen-rich atmosphere, it began to define just where life could survive. Imagine being a proto-amoeba drifting into a pocket of highly oxygenated water. Suddenly, your DNA starts to fire off sequences triggered by the random encounters of oxygen molecules accumulating within the cell itself. Proteins you need are not being made, because amino acids are being hi-jacked to make proteins you don’t need. Sure, a robust living cell can survive low levels of these kinds of mis-fires … but at a certain point, the cell expires when the internal chaos exceeds some threshold.

Enter stage right… “Hypoxia-Inducible Factors”, specifically a “proto-HIF - 1a”, the simplest protein that responds to Oxygen, and by regulating genetic transcription, protects cells from over-reacting to higher levels of oxygen diffusing into the cell from the environment.

HIFs - A new Way of Living

“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."

Pre-Cambrian Life Fades Out as Planetary Oxygen Levels Rise

“Hammarlund wonders whether the Ediacaran creatures, which disappeared at the start of the Cambrian, lacked this ability and therefore lived in the deep parts of the ocean because oxygen concentrations were more stable there.”

There’s Power in that Oxygen!

“. . . the development of the HIF proteins presented the “proper key to get at the gold mine,” Hammarlund said. It wasn’t until HIF came along … [and soon the more refined HIF-1a found in present-day invertebrates] … 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.”

Vertebrate Life Doubles-Down on Oxygen: HIF-2a

"As support for her theory, Hammarlund points to the evolutionary history of HIFs in animals. HIF evolved in animals, and it can be found in nearly all animal species; meanwhile, HIF-2α is unique to the vertebrates. “It makes sense when you think about it,” she said. “Vertebrates are bigger and have longer life spans than invertebrates. They’re better at maintaining their tissues in oxygenated environments.”

“When HIF-2α entered the picture, it would have given vertebrates even greater flexibility because their tissues could behave as though they were hypoxic regardless of their environment. This would have enabled them to form complex organs from diverse, highly specialized cells without regard for disruptive oxygen exposure. “HIF-2α was an even better tool for sustaining . . . pockets of hypoxic [high-oxygen] responses,” Hammarlund said. Stem cells could have resided in regions that were completely isolated from the oxygen gradients throughout the rest of a tissue.”

Invertebrates Limpet Along

“In contrast, she said, many invertebrates such as insects spend most of their lives as larvae living in low-oxygen conditions, and they can’t regenerate tissues as vertebrates can. Hammarlund thinks that invertebrates may not be as good as vertebrates at maintaining viable stem cells in their adult tissues for regeneration.”

It’s All a Coincidence?

“People who live at extremely high altitudes on the Tibetan plateau, for example, possess a mutation in a gene that encodes HIF-2α, causing the protein to function less effectively. That mutation also protects Tibetans from the otherwise detrimental health effects of living at lower oxygen levels, including altitude sickness, increased risk of stroke and pregnancy complications.” Is it just an accident that “…the HIF-2α phenotype is less necessary at high altitudes” where oxygen levels are always depleted, Hammarlund said.”


(system) #2

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