Cecilia Grimaldi
9th April 2021
It is an old question but that does not make it any less relevant: does size matter? For true love probably not, but when it comes to cancer risk the answer is not straightforward. Research recently published in the journal eLife has begun to untangle the intricated connection between an organism’s size and its risk of developing a tumour.
Cancer is complex and multifactorial. It originates from cell modifications triggered by a combination of genetic elements, environmental insults, and also ‘bad luck.’ Indeed, while a cell duplicates itself, the appearance of random errors in its DNA material might be sufficient to take it down a cancerous path. If we assume that each cell has the same probability of becoming cancerous and that cell sizes are similar in all animals, we should expect that larger individuals (made of more cells) have a greater tumour risk. This prediction has been confirmed within the same species, for example, in taller humans or larger dogs.
Interestingly though, the same body size to cancer risk relationship does not hold between species of a different dimension, a phenomenon known as ‘Peto’s Paradox.’ Scientifically, the explanation of why giants like whales show the same tumour risk as much smaller animals is straightforward: larger species must have developed better mechanisms to suppress tumours. But then comes the hard work of figuring out how these processes evolved – a problem as complicated as determining the causes of cancer itself.
Geneticists and biologists Juan Vazquez from the University of Chicago and Vincent Lynch from University at Buffalo investigated the Peto’s Paradox in African mammals (Afrotheria) that are, as the duo writes, ‘generally small-bodied, but also include the largest extant land mammals.’ Since these species originated from a common ancestor, their investigation involved following the evolution of genes associated with cancer risk in closely related species of different body sizes. The small-bodied animals included among others, armadillos, manatees, and hyraxes, while their larger relatives comprised Proboscideans like elephants, mastodons, and even woolly mammoths.
Quite unexpectedly, the two scientists found that the genomes of all these species contain double the copies of some genes known to reduce cancer risk (tumour suppressor genes). Remarkably though, larger species present also a unique increase in some additional tumour suppressor genes that confer extra protection against cancer onset. Chronologically, this genome’s modification emerged before the increase in body size, therefore enabling large-bodied animals to evolve without the disadvantage of a higher risk of cancer.
Remarkable follow-up questions raised by this work include whether similar mechanisms evolved in other large species, and if and how this knowledge could be applied to treat or prevent cancer.
Cecilia Grimaldi owns a doctoral degree in cell and developmental biology and she is now a science communicator in the making here at Imperial College. To sate her hunger for science and writing, she works as freelance writer and blogger for different science-related platforms. Reaching out to the general public is her main interest, as she believes there is a potential scientist inside each curious Homo sapiens after all.
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