Monday, December 17, 2012

Sheep red cell polymorphisms and anaemia (an old problem answered?) 

An improbably large amount of work, in many countries and laboratories, has gone into studying a few polymorphisms in the red blood cell biochemistry of sheep. Two of these polymorphisms are the variation in glutathione levels in the red cells of sheep and the variation in red cell potassium levels. The latter has probably attracted most attention, with a great deal of work on the existence and significance of genetic variation that divides flocks of sheep into high potassium (HK) and low potassium (LK) sheep. A lot of this focussed on possible relationships with production characteristics, such as wool quality.

I did my PhD in a blood physiology laboratory at the University of New England, Armidale, New South Wales, Australia. One of my supervisors was Professor JV Evans, who was the man who made the first crucial observations on HK and LK sheep and had a distinguished career as a blood physiologist.  He was an impressive and gifted scientist and a good supervisor.

I didn't work on the HK/LK model, but I did do quite a bit of work on the function of glutathione, the ubiquitous antioxidant tripeptide which helps protect red blood cells against oxidative damage. Among other things, I published a paper reporting that sheep whose red cells had higher levels of glutathione were more able to reduce methaemoglobin, the oxidised form of haemoglobin. I suggested that this might be one reason why some sheep would have high glutathione (GSH) levels. They would help the sheep deal with oxidative stress from plant toxins in the diet leading to effects such as haemolytic anaemia. Haemolytic anaemia is anaemia caused by the breakdown of red blood cells (haemolysis). 

What I want to suggest here is something that may be a new proposal. Namely, that the advantage of low potassium levels in red blood cells may relate to the fact that during a haemolytic attack, with red cells bursting and releasing potassium, the entry of potassium into the bloodstream is dangerous because it can interfere with the normal beating of the heart. Therefore it is reasonable to suggest that LK (low potassium) sheep would be at less risk because a bout of haemolytic anaemia would not result in as much potassium being released into the bloodstream as in the case of HK (high potassium) sheep.

In short, the LK genetic variant, like the high-GSH variant, might be an adaptation to the risk of haemolytic anaemia in flocks of sheep, which are constantly exposed to plant toxins.

It is relevant and interesting that cubozoans (box jellyfish) have recently been reported to exert their very rapid and fatal toxic effect by causing potassium to leak from red blood cells, thereby causing cardiac arrest. And many haemolytic snake venoms also operate in part at least by affecting heart function in a similar way.

I am not aware that the above suggestion for the adaptive function of the LK trait in sheep has been made previously, but I have yet to do a full literature survey. That being said, an immense amount of work has been done on the genetics and significance of the HK/LK trait in sheep red cells, and I cannot recall this suggestion having been made, at least at the time when I was doing red cell biochemistry during my PhD.


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