Tumour behaviour calls Cambrian-oxygen link into question

Exploration of the relationship between oxygen, stem cells and cancer might just challenge the story of how life as we know it came to be, according to new research published in Nature Ecology & Evolution.

About 543 million years ago, the most spectacular evolutionary event in the Earth’s history began: the Cambrian explosion. During this period, multicellular animal life began first to appear and diversify in staggering ways, producing such oddities as the aptly named Hallucigenia and the spiky Wixwaxia. 

The fossil record bears out this abrupt explosion of biodiversity, most clearly seen in the Burgess Shale in British Columbia, Canada. This vast fossil bed, holding within it the first appearance of modern animal phyla, seemingly without precursors, led the great Stephen Jay Gould to postulate his theory of ‘punctuated equilibrium’ – the idea that evolution is not always gradual, as Darwin imagined, but can sometimes undergo sharp leaps and bounds.

However, the cause of the Cambrian explosion has been much debated.

Previous hypotheses have centred around the idea that an increase in available oxygen may have triggered biological diversification. One 2013 paper published in the Proceedings of the National Academy of Sciences found that high oxygen environments promote greater ecological complexity, and argued on this basis that environmental oxygenation then satisfactorily explains the explosion of life in the Cambrian.

However, Emma Hammarlund, a geobiologist working at the division for translational cancer research at Sweden’s’ Lund University and guest researcher at the Nordic Centre for Earth Evolution at the University of Southern Denmark, is not convinced by this account. She notes that recent research has questioned the correlation between the Cambrian explosion and increasing atmospheric oxygen. 

“A heated hunt for the geochemical evidence that oxygen increased when animals diversified goes on,” she says, “but, after decades of discussion, it seems worthwhile to consider the development of multicellularity also from other angles.”

Instead, Hammarlund thinks a biological innovation might be key.

Hammarlund enlisted the expertise of Kristoffer von Stedingk and Sven Påhlman, both medical tumour biologists from Lund University.

“I wanted to learn what tumour scientists observe on a daily basis, in terms of tissue growth and how it relates to oxygen,” explains Hammarlund. “Tumours are after all, and unfortunately, successful versions of multicellularity.”

Together they investigated the relationship between oxygen and stem cell biology.

Stem cells, the pluripotent cells that can become any type of biological tissue, require specific oxygen levels, as do the cancer stem cells responsible for tumour growth. In particular, too much oxygen can wreak havoc with successful stem cell function. Stem cells, and cells that maintain similar properties, such as the tissues responsible for healing, as well as those responsible for tumours, generally require hypoxic, or low oxygen, environments. Certain vertebrate tissues even simulate hypoxia to allow them to work normally.

The team therefore hypothesises that the evolution of the biological innovation of stem cell properties might well have played a role in the diversification of life in the Cambrian. Such innovation not only could easily have happened in low oxygen environments, but might even have required them.

“Therefore, we flip the perspective on the oxic setting,” says Sven Påhlman, “While low oxygen is generally unproblematic for animal cells, the oxic settings pose a fundamental challenge for complex multicellularity.

“Surely, many people would intuitively disagree. But once you flip the perspective on the oxic niche and start to consider it as challenging for stem cell properties and tissue renewal, then puzzling observations from distant fields starts to fit together. And you can’t turn back.”