How Steller sea cow haemoglobin releases oxygen in the cold

A discovery that could lead to better preservation of donated transplant organs...
29 September 2023

Interview with 

Kevin Campbell, University of Manitoba


Red blood cells (erythrocytes) that contain the oxygen-carrying chemical haemoglobin


To a biochemical detective story about an extinct species of giant sea cow - called the Steller sea cow - that inhabited the frigid waters of the Arctic until the mid 1700s. How did an animal closely related to a warm-water dweller like a manatee, survive in sub-zero climes? Part of the answer lies in a tiny switch in its blood haemoglobin structure, which enables it to more efficiently release oxygen to tissues despite very low temperatures. The discovery is the work of the University of Manitoba's Kevin Campbell. He spoke with Dr Chris Smith…

Kevin - The story of this creature actually goes back to 1741, when it was discovered by naturalist George Wilhelm Steller, who was actually the naturalist on the ship, captained by Captain Bering that you may have heard of the Bering Strait and Bering Sea. They were shipwrecked on an island off the coast of Russia, a really cloud shrouded cold desolate place where they discovered Steller sea cows, or which became known as Steller's sea cows after Steller himself. These animals are very interesting in that they're very closely related to manatees and actually more closely related to the dugongs, but they were quite different, in that they were immense. They were whale-sized. They could be up to 10 metres long and maybe up to 10 tonnes. They lived along the rocky, desolate cold, wavy shores of these Commander Islands. And this is the last known population, but they had lived previously in the Alaskan Archipelago. And there's not the same food that is usually eaten by manatees and sea cows, which is seagrasses. They actually became adapted to eating mostly kelp.

Chris - And where have they gone?

Kevin - They were actually probably on their way out. So estimates are that when Steller discovered them, and again, this is the last remaining population of this species, that there were maybe 1000 to 2000 individuals at most, at that point in the early 1740s. This species was probably on its way out already though. Sadly they were hunted to extinction only 27 years after the discovery, mostly by shippers, people that would stop off of the islands and get some very tasty sea cow meat.

Chris - And so how is it that 250 years later you are able to study them?

Kevin - The conditions on these Commander islands, they're rather cool. And so some of the bones have remained washed up on shore, and they're now in museums. They're good enough quality. We were able to start getting some DNA and of course we targeted haemoglobin genes. But now even the last couple years, there's been a complete genome of the species.

Chris - Why did you go for haemoglobin?

Kevin - Well, haemoglobin is actually a really interesting molecule in the sense that it's the molecule that carries all the body's oxygen from the lungs to the tissues. So it's actually one of the few molecules that really links animals with their environment. Like most enzymes or most other chemical reactions, it kind of works a little bit better at offloading oxygen at warm temperatures, but not so good at cold temperatures. At really cold temperatures, it tends to hold onto oxygen really, really tightly. And this can be a problem for Arctic animals or Arctic mammals or birds, specifically because they often let their extremities really cool down too close to zero degrees if possible, so that they can minimise heat loss. And by minimising heat loss, it actually lowers their overall energy budget, so they actually have to eat less, right? So it's kind of like, imagine your house in winter. If you kept the windows open, you could keep your house warm, but your energy bill would be enormous. But if you can modify your haemoglobin so you can lower the temperature at which it's still able to offload oxygen efficiently or efficiently enough, they can save a lot of energy.

Chris - And you have, through the genome, got the genetic sequence, the recipe effectively for their haemoglobin. And does it show adaptations or differences?

Kevin - We studied three different Steller's sea cows, and we found a very unusual mutation in their haemoglobin. And we found a change in the beta subunit at a site that is perfectly conserved in all other mammals. At this one position, it's a lysine, which is a very strong, positively charged amino acid, but in Steller's sea cows, it changed from a lysine to glutamine, which is a neutral charged molecule.

Chris - And what do you predict that would do to the haemoglobin in the Steller's sea cow?

Kevin - Well, fortunately, there are some humans that carry the same mutation. It actually causes an increase in the overall blood oxygen affinity.

Chris - The problem that the Steller's sea cows are grappling with is, in the cold, they want to give up oxygen from their bloodstream into their tissues, but without having to have a ferocious rate of blood flow to get enough oxygen in. So they want their haemoglobin to give it up readily. If it increases the affinity, this change of the haemoglobin for oxygen, does that mean the haemoglobin hangs onto it better? In which case, how does that serve their purposes?

Kevin - That's the one single big difference between human haemoglobin that has this change and Steller's sea cow haemoglobin that has this change. In humans, this effect causes the affinity to go up. But in Steller's sea cows, this change causes their blood oxygen affinity to actually go down. And the second thing is, it takes the same amount of heat to break this energy bond between oxygen and the haemoglobin, regardless of the haemoglobin type, right? Whether it's from a reindeer, a Steller's sea cow, a woolly mammoth, or a human. However, these cold adapted species tend to have some modifications in their haemoglobin. So, as I mentioned, it takes heat to break bonds, but haemoglobin doesn't only just bind oxygen, it's able to bind other molecules. And we have an organic phosphate in our red blood cells called phosphoglycerate. And it's also able to bind to this molecule. But these molecules tend to bind to haemoglobin when it is ready to offload its oxygen in the tissues. And the interesting thing is when these molecules bind to haemoglobin, it actually releases heat. So in colder temperatures, these haemoglobins from these cold adapted species tend to have these modifications where these other molecules can bind to haemoglobin, and that releases some heat, and then that heat can actually get donated or kind of shifted over to where the oxygen is found. And it's a little, almost a self heater to help break that bond between oxygen and the haemoglobin in the cold tissues of these species. But the change in the Steller's sea cow was really perplexing to us at first because it actually lowers the amount of phosphoglycerate binding to the molecule, which is what we think usually gives the heat. But this change, as I mentioned, is found right in the central cavity of haemoglobin. And so what this change does itself is it lowers the amount of heat required for this change. And so this kind of gives that energy itself to break the oxygen bond. So it's the precise opposite as what we find in most other mammal species. They're doing a different mechanism, but the end goal is they're able to offload oxygen. Pretty good at cold temperatures.


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