Biochemical Soul Musings on Nature, Science, Evolution, Biology, and Education


Adaptation of the Week – Channichthyidae Icefish Blood and Antifreeze

I owe the following example of evolutionary adaptation to the always amazing evolutionary and developmental biologist Dr. Sean B. Carroll, from his lecture "Making of the Fittest" for the Darwin College - Darwin Lecture Series, available at iTunes U (I highly recommend everyone give it a listen).

The Red Blood Cell-less Icefish © Dr Julian Gutt and Alfred Wegener Institute

The Red Blood Cell-less Icefish © Dr Julian Gutt and Alfred Wegener Institute

Imagine that you are a fish - exothermic and thus unable to regulate your own body temperature - and the contingent foibles of natural history have all conspired to leave you and your kind in the frigid oceans of the Antarctic just as they are beginning to reach the freezing point (10-14 million years ago).

You like the cold and are well adapted for it, but these temperatures are beginning to give even you - a master of the cold - the icthy chills.

Now imagine that the hands of mother nature have given you the tools to change your own genetic code, and thus your nature, allowing you to make yourself even more suited for waters that are 2 degrees celsius below the freezing point of pure water.

What would you do? Would you inject your DNA with a molecular antifreeze? That seems like a reasonable addition - one we will get to momentarily.

But if you were a genius of bioengineering would you reach out a molecular scalpel and hack away the genes that allow the production of red blood cells, hemoglobin, and myoglobin, leaving only molecular fossils behind?

Icefish Larva

Icefish Larva © Uwe Kils

It doesn't seem like a particularly well thought out plan. But then again, neither you, the fish, nor mother nature are genius bioengineers. Fortunately for life, the forces of evolution still manage to get the job done, however sloppy the end results (yes, technically the job is never done - forgive my metaphor wearing thin).

In fact, natural selection performed just such a feat somewhere around 8.5 million years ago in the ancestors of a flock of related species in the Antarctic: the Channichthyidae icefishes (also known as crocodile icefishes or white-blooded fishes).

As we all know, liquids tend to become more viscous in the cold. Just compare maple syrup before and after refrigeration. Blood viscosity would have no doubt been an issue in the ancient ice fish ancestors, or at least one that could be improved upon. Normal vertebrate blood is filled with big, round, and red blood cells coursing through the blood vessels. Now imagine lowering the temperature of the blood below the normal freezing point of water - that's bound to create some significant resistance.

But aren't erythrocytes critical for carrying oxygen? How could an organism just dispense with them completely? As many scientists know, one of the great things about really cold water is that it can be packed with oxygen. Such is the case with the waters of the Southern Ocean, which are saturated with oxygen.

Thus, it seems that at some point, the icefish ancestors developed mutations in the pathways that result in red blood cell production. Furthermore, the species eventually acquired a deletion in the key genes of red blood cells: the alpha and beta hemoglobin genes. No longer could this fish produce hemoglobin.

As is often the case with evolution through loss of gene function, the deletion wasn't perfect. Almost all vertebrates have both hemoglobin genes lying next to each other within the genome. In most Channichthyidae icefishes, the beta hemoglobin gene has been completely deleted, along with all but the truncated end of the alpha hemoglobin gene (interestingly, these fish have lost their myoglobin gene as well)1. To quote the original paper by Near et al.:

"Despite the costs associated with loss of hemoglobin and myoglobin in icefishes, the chronically cold and oxygen-saturated waters of the Southern Ocean provided an environment in which vertebrate species could flourish without oxygen-binding proteins."

The upshot of all this is that the icefish has completely clear blood lacking in any erythrocytes - and they are the only species of vertebrates to have such a trait.

Normal 2 globin genes vs. lost icefish globins - modified from Near et al 2006

Normal two hemoglobin genes vs. lost icefish hemoglobins - cropped figure from Near et al 2006

Of course, a few other supporting traits evolved as well. Their hearts are significantly larger than other fish hearts, and they pump 4 to 5 times larger volume of blood per stroke2. Their capillary beds have become much more dense as well to make sure all their tissues get adequate oxygenation. Of course, like amphibians that breathe through their skin, with the loss of red blood cells, those that were better able to absorb oxygen tended to outperform their cohorts. Thus they became scaleless as well.

As if these adaptive feats weren't cool enough (pun intended), the antarctic icefishes have evolved their own antifreeze as well3,4. What's amazing about this antifreeze (an Antifreeze Glycoprotein - or "AFGP") is that it represents one clear cut case in which a gene with a specific function has evolved into a separate gene used for a completely different function in a novel way. In the case of the icefish, the ancestral gene was a trypsinogen (a pancreatic digestive enzyme), which has been mutated and co-opted to be secreted and distributed throughout the body to act as an antifreeze. Specifically (for you biologists out there), the 5' secretory signal and 3' UTR sequences of trypsinogen were tacked onto an amplified nine nucleotide sequence from within the trypsinogen precursor to create the novel antifreeze peptide.

So here we have in the icefish's adaptation to the cold, at least one case of de novo creation of a novel gene with a new function from an old gene, as well as the loss of two other genes that have left genomic fossils behind to whither in the weathers of time.

It may not be the cleanest or best engineered solution to the problem of living in an Antarctic Hell (or perhaps Heaven from the perspective of the fish), but this messiness of evolution is precisely what makes it so incredibly beautiful.


  1. Near T.J., Parker S.K.,  Detrich H.W. A genomic fossil reveals key steps in hemoglobin loss by the Antarctic icefishes. Molecular Biology and Evolution, v.23, 2006, p. 2008 - 2016.
  2. William C. Aird. Endothelial biomedicine. Edition: illustrated. Published by Cambridge University Press, 2007
  3. Chen L., DeVries A.L., Cheng C-H. C. Evolution of antifreeze glycoprotein gene from a trypsinogen gene in Antarctic notothenioid?fish. PNAS, April 15, 1997 vol. 94 no. 8 3811-3816
  4. Chen L., DeVries A.L., Cheng C-H. C. Convergent evolution of antifreeze glycoproteins in Antarctic notothenioid fish and Arctic?cod. PNAS, April 15, 1997 vol. 94 no. 8 3817-3822
  5. Top image © Dr Julian Gutt and Alfred Wegener Institute
  6. Icefish larval image by Uwe Kils

Previous Adaptations of the Week:

  1. Timber Rattlesnake Camoflage
  2. The Aye-Aye’s Freaky Finger (I’ve Been Cursed by an Aye-Aye!)
  3. Flatfish Eyes & Recapitulation Theory
  4. Bird/Crocodile Symbiosis?
  5. Insect Dorsal Ocelli