Ten genes help Tibetans thrive over 10,000 feet

Chris -  Also in the news this week, researchers have discovered why Tibetans who have a taste for the high life are much better able to tolerate the low oxygen conditions that you find at higher altitude, compared with their lowland living counterparts.  It turns out that they carry at least ten unique genes that enable them to do it.  To tell us more, from the University of Utah, is Tatum Simonson.  Hi, Tatum.

Tatum -  Hi. 

Chris -  If you could tell us first of all, what was the reason for doing this study?  What were you aiming to find out?

Tatum -   We were interested in identifying the genetic basis for high altitude adaptation, what's interesting is that several research groups have done an excellent job characterising sets of physiological traits that are unique to native high altitude inhabitants.  These studies have suggested that populations have adapted to this extreme environment, but the genetic basis wasn't entirely known.

Chris -   So in other words, by living at high altitudes for many generations, these individuals must've accrued some kind of genetic changes that made them much better adapted to living there than say, me.

Tatum -   That's exactly right.

Chris -   So, how do you approach that problem?

Tatum -   It's only recently that we've been able to actually look at our genetic code, or DNA, and by looking at single changes in the DNA sequence, we can identify regions that have been subject to what we call natural selection - the idea being that these variants have been beneficial for some particular reason in a particular environmental setting, and have been passed on through the generations, and allowed individuals to survive.

Chris -   The thing is there are three billion letters in the human genetic code.  How do you home in on the bit that you think might be important in this instance?

Tatum -   So what we used was an approach that looks at what we call Single Nucleotide Polymorphisms (SNPs) or tags across the entire genome and we identified blocks or regions of the genome that exhibit a certain signature.  The signature that we see with natural selection is that basically, you have a whole region that's increased rapidly in the population.  That leaves behind a certain sign that we can look at and compare it with the rest of the genome.  It really stands out as a striking signal for us to then go in and analyse.

Chris -   So in other words, if you take people who live at high altitude in Tibet and have done for many generations and you compare them with the rest of the world who don't live at those kind of altitudes, and you're looking for specific hot spots in their DNA that keeps cropping up time and time again in the Tibetans but not in other people.  This points you towards thinking in that region of the genome, there must be some beneficial change that helps these people to survive where they do.

Tatum -   That's exactly right and we were able to do that by comparing the Tibetans with publicly available information on both Japanese and on Chinese populations.

Chris -   Those populations presumably being significant because they're going to be relatively closely related in terms of human ancestry to the people you're studying.

Tatum -   Right.

Chris -   So you can iron out a lot of other changes.

Tatum -   Exactly and they've typically lived in lowland regions which is key for our study.

Chris -   And when you did this, what did you find?  Did you home in on some genes that you do think enable these people to survive where I would struggle?

Tatum -   Yes, so as you mentioned, we have at least ten genes that we've identified and what's interesting is that two of those genes were actually correlated with a certain physiological trait which is unique to Tibetans.  That is the fact that Tibetans exhibit haemoglobin concentration which is similar to somebody say, living in London - so somebody at or near sea level.  Yet, they're all the way up at 4,000 metres.  Any non-adapted individual would increase their haemoglobin to compensate for the oxygen-deprived environment.  So, when we compared two of our selected regions of the genome to the haemoglobin levels we measured, we found that two of them actually are associated with this decreased haemoglobin level.

Chris -   So, in other words, if I went up to a very high altitude, I would compensate for the low oxygen by increasing the amount of haemoglobin.

Tatum -   Right.

Chris -   This helps me to get more oxygen around my body but has negative consequences because my blood's going to become thicker, stickier, gloopier.  Therefore, I'm more likely to have consequences like high blood pressure and heart attacks, and strokes.

Tatum -   That's right.  That's exactly right.

Chris -   But the Tibetans don't?

Tatum -   But the Tibetans don't, yes.  This area definitely needs more research.  We know that this isn't happening but it also could be a side effect of something else that's been advantageous and selected for - so that they don't need to increase their haemoglobin because they're already so efficient, perhaps through some other mutation.

Chris -   And I guess, just to finish off, the benefit of doing this kind of work is that there are situations where people who don't live in Tibet above 4,000 metres nonetheless have very low levels of oxygen in the bloodstream; I'm thinking people who have lung problems, lung infections, blood clots on the lung, maybe their whole body is exposed to low oxygen because of drowning or carbon monoxide poisoning or something.  Understanding therefore how people cope naturally in these environments might provide a clue as to how we develop medical therapies to help people who are acutely in that situation.

Tatum -   Yes, that's exactly true.  So, this information can definitely help researchers develop therapies or even drug targets for people who have various amounts of oxygen-deprived disease or that sort of a thing.

Chris -   Is that where you're going next with this?

Tatum -   We do.  We do hope to go forward.  The idea being if we understand why people do well then perhaps we can help those who aren't doing as well at high altitudes.

Chris -   Including one or two climbers perhaps.

Tatum -   Yes, that's true.

Chris -   Tatum, thank you very much.  That's Tatum Simonson.  She's from the University of Utah and she's published that work this week in the journal Science.