Living high on the hob

Funny how things happen in threes.  On Monday last week I was in Athlone getting a free dinner for my part in landing a mentoring award for a mentor of mine.  That was a life-time mentoring prize despite her having a chunk of time to run before retirement let alone end-of-life issues.  The winner of the young mentor award was a dynamic chap from UCD called Cormac Taylor who works on the biology of hypoxia - coping with lack of oxygen in the tissues.

On Thursday, I was off-site from the Institute on my way to Dublin to hang out with my old Comparative Immunology crew.  Rather than waste the bus-journey in collar-drooling sleep, I brought along my copy of the Physiology Colouring Book to see if I could improve my lectures on the circulatory system.  I was reading about why haemoglobin is constructed in such a way that it can carry four molecules of oxygen.  Not only that but if tends to carry either four molecules or none, being able to take a full load at the lungs and blurping all the oxygen off when the red blood cells reach the tissues. The chapter also talked about the crucial importance of NO nitric oxide in controlling the delivery of oxygen to the tissues notably by 'vasodilation' increasing the diameter of blood vessels and so increasing flow.  Nitric oxide is essential for re-perfusion of tissues after the hypoxial effects of ischaemia.

A few hours later over lunch, hypoxia came up again in talking about the way in which humans adapt to the desperately low amounts of oxygen available at high altitudes in places like the Himalaya, the Andes and the Ethiopian highlands of East Africa.  It turns out that in each location humans have developed quite different ways of dealing with the problem. Tibetans breathe faster than their nearest lowland relations and also generate more nitric oxide which leads to vasodilation; so they cope by pushing more loaded haemoglobin through the system. Quechuas in the Andes, by contrast, breathe normally but have haemoglobin with a higher oxygen carrying capacity. Ethiopian Highlanders show neither of the adaptations but have developed another way of cracking the epidemiological nut.  As with all systems in the human body, numerous genes are involved in the relevant biochemical pathways and so there are several possible changes that will enable sustained high-altitude living. Each of these distantly related groups has evolved a different solution: a random mutation in one gene which helped that person survive better and reproduce more in the hostile environment of the highlands. That gene variant propagated rapidly through the whole population.
Indeed the rate of changes in the frequency of the EPAS1 gene in Tibetans has been the fastest ever recorded in a human population. There is evidence that natural selection is ongoing in the Tibetan population, where women estimated to have genotypes for high oxygen saturation of hemoglobin (and less physiological stress) have higher offspring survival". Cynthia Beall [R high on the hoss] is the Go To Gal for this stuff. All of these oxygen metabolism genes are of interest to athletes and will doubtless be used in the literature for various quack cures and performance enhancing regimes.