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The Chilly Mammoth

By Eliza Gray

Photo credit: Pixabay,Paint X

“Sub-arctic temperatures will force us underground for a billion, billion years!” Fans of Ice Age will recognise this quote from the fictional sloth Sid to Manny the woolly mammoth. Whilst the two characters survived the sub-zero temperatures along with their friends,a sabre tooth tiger,a possum and a pre-historic squirrel, the same lucky escape cannot be said for the extinct non-fictional woolly mammoth (Mammuthus primigenius). The woolly mammoth would have become extinct a long time before that however, if it weren’t for an extraordinary adaptation to the sub-zero temperatures in it’s haemoglobin.

Haemoglobin is a vitally important protein found in red blood cells, and is present across many life forms. Its primary function is transport of oxygen in the blood, effectively binding and releasing oxygen to provide a supply of cellular oxygen to metabolically active tissues. As with most proteins, haemoglobin relies on very specific structural protein folding of the haemoglobin subunits in order to function. For example, small scale changes in the folding of the four protein subunits in haemoglobin can determine how much oxygen is released to the surrounding tissues. Because of this, haemoglobin is extremely susceptible to environmental changes in temperature and pH, which can detrimentally affect the protein’s folding and thus functioning if they deviate from their optimum ranges in the body.Unsurprisingly, the optimum temperature for human haemoglobin functioning is around 37°C, that of human body temperature, for example. Importantly, decreasing temperature much below the thermal optima can cause haemoglobin to release fewer oxygen molecules because it binds to it more tightly, or in other words, has a higher affinity, or liking for oxygen at lower temperatures, so binds to it more tightly.

Now, picture the woolly mammoth in sub-zero temperatures, and the freezing temperature of its limbs as it trudges through the snow and ice. See the problem? If the mammoth’s temperature in its appendages falls below that of the body core, it raises the possibility of massively reduced oxygen offloading to the tissues because of the high haemoglobin oxygen affinity at low temperatures.

Scientists recently uncovered how the mammoth overcame this predicament using DNA from a 43,000-year-old permafrost preserved mammoth. The DNA sequence of the α and β haemoglobin protein chains in the closely related African and Asian elephant species were already known, and scientists were then able to sequence the 43,000 year old mammoth DNA, and compare this sequence to the known sequence of the modern elephant. Using these sequences, they were able to predict the sequence of amino acids in the haemoglobin proteins of mammoths and modern elephants and compare these sequences to identify any sequence changes. Interestingly, they found that the α globin chain differed between the two in one amino acid, and the β chain differed in three amino acids [1].

In order to see the effects of these amino acid differences on haemoglobin function, researchers introduced the genes for synthesis of modern elephant haemoglobin into E.coli, a bacterium that would subsequently express the haemoglobin genes and produce the haemoglobin protein. Using site-directed mutagenesis, the modern elephant genes were mutated in the specific location, so that the gene resembled that exactly of the mammoth haemoglobin gene. This meant that E.coli bacterium were able to express the mammoth haemoglobin protein so that scientists could study its functioning. Researchers found that the mammoth haemoglobin in contrast to modern elephant haemoglobin was comparatively insensitive to low temperatures. This meant that when haemoglobin was circulating in the low temperature of the limbs, it was able to release oxygen to allow metabolic functioning, an adaptation that has subsequently been lost from modern elephants which live in much warmer climates. [1][2][3].

So next time you complain about the cold, spare a thought for the extremes the woolly mammoth had to go to to survive, and be pleased you can go inside and put another pair of socks on!


References

  1. R. Hill et al.,”Animal Physiology”,3rd ed, 2012,Chapter 24,Sinauer Associates
  2. K L Campbell et al., Nature Genetics, 2010,42,536-540.
  3. Y Yuan et al.,Biochemistry,2013,52,8888-97.

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