Faculty of Medicine

Lund University

Tumour biology provides new hypothesis about the evolutionary success of animals

2018-03-12

Geologists have for long claimed that the emergence of animals was enabled due to increasing oxygen content in the atmosphere, but this hypothesis has been difficult to prove. Researchers at Lund University have now adopted an interdisciplinary approach to the issue and presented a new hypothesis as to why animals managed to diversify approximately 543 million years ago. With the help of clues from tumour biology, the researchers argue that a biological key ensured the animals’ success. The findings are published in the journal Nature Ecology & Evolution.

sven pahlman och emma hammarlund
Sven Påhlman och Emma Hammarlund

Lund researchers have used clues from the field of tumour biology to address the historical question of why animal emerged so late and dramatically. Photo: Emma Hammarlund and Sofie Mohlin.

The new hypothesis entails that the dramatic arrival of animals originated in a revolution in the animal’s own biology and not in a change in the Earth’s surrounding chemistry. The hypothesis may also have further significance for how we look at the ability of different animals to live in oxygenated environments and perhaps also for the way we consider cancer as an evolutionary consequence of our own ability to live in an oxygenated environment.

Taking an evolutionary approach is not something a cancer researcher normally does, even though tumour development is generally seen as an evolutionary process. It is also not common for a geobiologist to adopt a cell perspective. However, after joining their expertise, the two Lund researchers Emma Hammarlund and Sven Påhlman were surprised to find that the human ability, over millions of years of evolution, to regenerate tissue despite high levels of oxygen, had not caused reflection before.

“There are probably many who would intuitively disagree. But once we turned the binoculars around, it was possible to see how our observations are related. Then there was no going back”, says Sven Påhlman, professor of molecular medicine at Lund University.

Historical focus on high level of oxygen

The Earth is 4.5 billion years old, but it took almost 4 billion years before multicellular life – in the form of animals – diversified into new types of ecosystems with great biodiversity. The animal diversification that occurred during a relatively short period was dramatic and is therefore referred to as the Cambrian explosion (see the fact box below).

Geologists have for long assumed that the Cambrian explosion was initiated by an increase of oxygen in the atmosphere. However, finding convincing evidence to support that the oxygen level rose during the Cambrian period specifically proved difficult. In contrast, research now shows that dramatic changes in air oxygen levels occurred both before and after the Cambrian explosion, but not in fact at the point when the wealth of animals began to emerge. Furthermore, other studies show that simple animals require a surprisingly low amount of oxygen. Therefore, the increased understanding of the Earth’s history and the origin of life does not support the old explanation that a difference in surrounding oxygen levels started a revolution among animals.

“We’ve practically banged our heads against the wall to find geochemical evidence of how oxygen levels increased at the point when animals diversified so dramatically; instead, we should’ve considered the development of multicellularity”, says geologist Emma Hammarlund, researcher at the Division of Translational Cancer Research at Lund University. Her most recent employment was at the Nordic Centre for Earth Evolution, which is a collaboration between the University of Southern Denmark and the Swedish Museum of Natural History.

Clues provided by tumours

In order to understand more about the conditions for multicellular life, Emma Hammarlund contacted tumour biologist Sven Påhlman, at the Department of Laboratory Medicine at Lund University, who conducts research on oxygen deficiency in tumour cells.

“Because geologists like myself are not able to reconstruct the Cambrian explosion in the laboratory, I wanted to understand more about the multicellularity that tumour researchers see every day, and what they know about how oxygen affects the formation of tissue. Tumours, after all, are a successful kind of multicellularity”, explains Emma Hammarlund.

Emma and Sven, together with tumour biologist Kristoffer von Stedingk at the LU Division of Paediatrics, have tried to answer the historical question of why animals emerged so late and dramatically, by looking at clues from the field of tumour biology.

A common key to the oxygenated energy-rich environment

When faced with this evolutionary puzzle, the researchers tested whether knowledge of tumour success can also explain something about the animals’ success during the Cambrian explosion.

“Generally, we see oxygen deficiency, or hypoxia, as a threat but forget that it, to some extent, is also a necessity for multicellular life. Our stem cells, which form new tissues, are extremely sensitive to high oxygen levels and, therefore, the cells have different systems in place to handle it. This is evident in tumours”, says Sven Påhlman.

By studying the ability of tumour cells to mimic the properties of stem cells, Sven Påhlman’s research team discovered that tumour cells simply kidnap specific systems in the cell to circumvent the effects of high oxygen levels. As a result, the tumour cells may acquire stem cells properties, even though they are surrounded by the high oxygen concentrations that are also present in the body. The researchers argue that this ability is one of the keys to the animals’ great success.

“The ability to construct stem cell properties despite high oxygen levels can also be found in normal tissue. So we turned the perspective around: low oxygen is not a problem, but for complex multicellular life, high oxygen is a challenge as it causes tissue-specific stem cells to mature prematurely”, concludes Sven Påhlman.

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