Adventures in mountain genetics – By Jelena

What the ACE gene actually looks like

My name is Jelena, I’m a genetics researcher at Cambridge University, and this summer I’m about to climb Kilimanjaro for the very first time. Now, you wouldn’t think those last two things are related. But as a professional geek, I couldn’t resist researching the health background of the trip before signing up.

With a bit of training, it didn’t seem like fitness would be much of a problem, as the group of us who are going are all reasonably fit people in our twenties. However, altitude was a concern, particularly since Cambridge is a perfectly flat town situated at around 7m above sea level, so we’re not exactly acclimatised in any way. The possible prospect of Acute Mountain Sickness seemed a bit terrifying. But also more pragmatically, signing up to an expensive trip where you might randomly be very sick and not make it to the top just didn’t sound that much fun.

In general, this led to the decision to do the climb slowly enough to allow time for altitude acclimatisation (we’re going for seven days). But I was also very excited to find out that there was a lot of genetics research into altitude sensitivity. I happened to find out about it from a great talk by Professor Hugh Montgomery, who is an expert on the genetics of human fitness, and in particular on the physiological response to low oxygen conditions.

I was particularly excited to find out that there was a single gene that predicted with high reliability how people reacted to low oxygen conditions. The gene in question is called the ACE gene, and it is present in two different forms in humans—for this gene, you can either have an ‘I’ or a ‘D’ version of it. Because we inherit two versions of each gene (one from each parent), this means that you can have three potential versions of this gene: II, ID, or DD. As well as giving you an idea of altitude sickness susceptibility, this is also an interesting fitness gene. Genetically, there is a bit of a trade-off between strength and endurance, and this is a gene that tells you whether you’re more of a strong bodybuilder type, or more of an endurance person such as a rower, cyclist, or long-distance runner. Or alternatively, something in between.

Some data I personally found very compelling was that, conveniently for us, scientists had studied this gene in people climbing Kilimanjaro. They looked at people attempting to reach the summit in four days (which in general is really not recommended), and tested how many people with each gene type reached the top. The DDs, your strong body-builder types with bad low oxygen tolerance, only reached the summit 40% of the time. The IDs, who have a mixture of strength and endurance genes, reached the top 60% of the time. The IIs, on the other hand, are the endurance people with low oxygen resistance superpowers—this group managed to reach the summit almost 100% of the time, despite the very short time for acclimatisation.

In a more serious context, the IIs also had much better clinical outcomes in emergency medical situations where they were oxygen deprived. So you would wonder why not everyone has the II genotype. This is a classic genetics trade-off; the DDs are stronger and build muscle faster, which is advantageous in other circumstances. And the low oxygen thing might just never come up if you’re lucky. There is no such thing as ideal genetics—what we actually have are different genetics that are advantageous for different circumstances.

Now, given enough time, anyone can reach the summit, so you shouldn’t let your genes stop you. However, it seemed like an interesting data point to add to trip planning. For example, if you’re particularly at risk, you can make sure that you definitely add an extra day or two of acclimatisation, and don’t forget those altitude sickness pills. These are sensible precautions for everyone, but how much they matter does depend on your genetics. Also, we were curious! So we were all very excited to find out that PlayDNA already tests for the different versions of the ACE gene.

Despite being a geneticist, I’ve never tested any of my own genes before this. I think genetic testing should be approached carefully, and that people should only be tested for things that they want to find out about, while aware of the impact of the information. However, in this case I had no qualms; ACE is a fitness gene, which reveals general-interest information rather than medical conditions. The opportunity to discuss genetics with my friends also made me very happy. Something that is harmless but personally relevant to people is, I think, the best way to get thinking about these concepts.

It was also fun for me to see how the science was applied outside a research context. And it was certainly an exciting day when the beautiful PlayDNA testing kits arrived in the mail.

Six of us got tested for the gene, including my partner and I. We had some expectations about the results—since my partner is a great sprinter and tires himself out quickly, while I’m more of a moderate long-distance person, we definitely expected that he would come out as a DD, and I would come out as an II. We were less sure about our friends, although we suspected that our friend who had done some significant long-distance cycling in the past would come out as an II.

We were very excited when the results arrived. It feels like something between buying a lottery ticket, and maybe some of those personality self-tests. It’s just fun finding out something about yourself and your friends. And they were beautifully presented too. While I personally recoil a bit from associating gel images like this one with my PhD and late nights in the lab, I can also see how it’s a cool and artistic way of communicating the test results. Also, unlike other companies based on a similar premise, it pleases me that this one communicates how the science is actually done. Sam even told us how the DNA extractions went, and was happy to explain the test validation process.

In terms of the test results: it turned out that we had two II superpower people in our midst, including our long-distance cycling friend, but that sadly I wasn’t one of them. Much to our surprise, my partner and I both turned out to be IDs. We certainly wouldn’t have guessed that we have the same genotype, but it brings home the point that not everything is in your genes—maybe we just approach exercise differently. And it’s true that IDs have both power and endurance potential, and it’s up to individual people how they work with that and where they take it. There was also a third ID, and a single DD person in the group.

Even though I’ve thought about it a lot, and I deal with this type of research daily, it was still a little bit funny seeing the results on paper. I mean, you can have all sorts of ideas about yourself, but actually having them tested, and having a result in black and white that you can’t change is kind of different. I don’t believe that genes should limit us and inform how we run our lives. Yet a part of me was disappointed to not have won the lottery for the low-oxygen trait. Serious body builders may have a similar reaction if they don’t have the DD version—despite the oxygen disadvantages, it makes it much faster to get strong and build muscle. Once you find out for sure, there isn’t really anything you can do about recasting the genetic dice.

But the genes are just the beginning. And they’re just one factor and piece of information. Where we go, and who we become from there, is still entirely up to us.

In accord with this, who is actually coming on the trip was mainly determined by factors other than their genotype, such as money and holiday time. Though one of the IIs was also nudged a bit by their newly discovered superpower. In the end, four of us are going: two IDs and two IIs. Since our DD isn’t coming (for reasons other than genetics, we swear), we won’t be able to bring you tales of overcoming genetic determinism this time round. But we still await with curiosity how our genetics will play out when, this August, we hit the big mountain.

With best fitness-and-mountain-climbing wishes for all,

Jelena, ACE I/D heterozygote

Written by Jelena

Saturday, April 19, 2014