While preparing some size-comparisons of marine life for Week 3 of our free Massive Open Online Course on “Exploring Our Oceans”, I was particularly struck by how whales are astounding animals. An adult blue whale can have a body mass of ~150 tonnes. That’s around twice the body mass estimated for the largest known dinosaur ever to walk the Earth, and equivalent to the body mass of around 2000 people (i.e. the population of a village, perhaps).
But what is really astounding about that huge body is that it grows from a single fertilised egg cell, just as our bodies do, but in much the same time as our bodies do. As I’ll try to explain here, that almost makes blue whales impossible animals. But thanks to the recent sequencing of another whale’s genome, perhaps there is a speculative yet intruiging connection to ponder between large body size in whales and breath-hold diving ability.
To attain its huge size, a blue whale’s body grows very rapidly compared with our bodies. A blue whale calf may have a body mass of around 3 tonnes at birth – and yet the time it takes to develop from a single fertilised egg cell (perhaps less than a year for a blue whale) is not very different to our gestation period of 9 months. And after birth, blue whales probably approach their adult body size by their teenage years, also rather like us.
So blue whales have a phenomenal overall growth rate: from single fertilised egg cell to ~150-tonne leviathan within a couple of decades. And that means that they must experience phenomenal rates of cell division. In general, the individual cells of a blue whale’s different tissues are not substantially larger than those of the same tissues in other mammals, so they don’t get large by having large cells, but by having lots of them (although, as an aside, some of the single nerve cells in a blue whale’s spine are incredibly long, and may stretch by 3 cm per day to grow without dividing).
Cell division involves a risk. Every time a cell copies its DNA during division, there’s a chance of errors creeping into the copy. If an error arises at just one of many key places in the genetic code, it can trigger the development of different forms of cancer (although there are also mechanisms that try to spot the errors and correct them). Every cell division is a roll of the dice – and blue whales therefore seem to roll those dice more times than any other mammal.
So whales embody an apparent paradox for biologists, as this blog post by Carl Zimmer summarises nicely. Whales do get cancer, but if blue whales were just like us, then all of them should have colorectal cancer by the age of 80 (and probably other cancers too), yet most of them do not. Instead, they are an example of “Peto’s paradox”: the observation that cancer rates don’t seem to correlate with larger average body sizes among mammalian species.
Carl Zimmer’s excellent post summarises ideas about how whales might resolve Peto’s paradox, and ends by mentioning not having “a single fully-sequenced genome of a whale or a dolphin for scientists to look at” back in 2011. Well, three years is a long time in the field of genomics, and at last we do! Yim et al. (Nature Genetics, 46: 88-92, 2014) have now sequenced the genome of a Minke whale, and compared it with sequences from a fin whale, bottlenose dolphin and a finless porpoise, along with cows and pigs.
What their comparative genomic analysis shows is that some gene families appear to have expanded in the cetaceans, while others have reduced, compared with pigs and cows. Gene families associated with body hair and sense of taste or smell appear to be reduced in whales. But whales have expanded families of genes involved in combating oxidative stress in cells. Yim et al. suggest that these expanded gene families may be adaptations for prolonged breath-hold diving, which results in hypoxia (low oxygen conditions) in tissues.
During hypoxia, cells accumulate “reactive oxygen species” – potentially damaging forms of oxygen, such as hydrogen peroxide – and Yim et al. show that whales have expanded gene families in particular to cope with reactive oxygen species. Reactive oxygen species are also involved in the development of cancer, and hypoxia tolerance and cancer resistance have been linked in blind mole-rats, which live in low-oxygen conditions in their burrows. So what particularly strikes me initially from Yim et al.‘s study is that whales appear to have expanded families of genes that cope with hypoxia and reactive oxygen species – and they also embody Peto’s paradox.
This then poses a couple of speculative questions: did whales evolve prolonged breath-hold diving ability first, and in doing so acquire expanded gene families to combat oxidative stress, which might then have enabled the evolution of large body size by reducing cancer risk from reactive oxygen species?
Or did the evolution of whales first involve a selection pressure for large body size, resulting in the evolution of expanded gene families to combat oxidative stress, which were then co-opted to enable prolonged breath-hold diving?
In other words, I wonder which came first in cetaceans: prolonged breath-hold diving, or large body size? Estimating the body size of extinct cetaceans from incomplete fossil skeletons is tricky (as is inferring their diving capability), and of course it is possible that the two arose contemporaneously under simultaneous selection. But an analysis by Pyenson & Sponberg (Journal of Mammalian Evolution, 18: 269-288, 2011) indicates that extremely large body size may be a relatively recent phenomenon in the evolutionary history of the baleen whales (which include the blue whale).
There’s a lot of blog-post-arm-waving here, and I’m very conscious of straying outside my own area, into the fields of cetacean evolution and cancer biology. But perhaps it’s interesting to consider whether a reduced cancer risk in whales, implied by their huge body size, might involve a spin-off from their adaptations for extreme breath-hold diving – or vice-versa.
Jon Copley, May 2014