Vegetarianism could be in your genes

What has been going on in the headlines of genetics over the past month? But, whilst we can definitely cover that, could we also take it a step further? Because it’s all well and good to look at a genetic study and see that the presence of gene X leads to disease Y. But in something as complex as the human body, which has over 20,000 genes, how can anyone really say with confidence that a certain gene or gene cluster is solely responsible for something as huge as a vulnerability to a disease. So what are the questions that actual geneticists ask when they see the headlines?

Aylwyn - I'm Aylwyn Scally. I'm a researcher in human evolutionary genetics here in the Department of Genetics in Cambridge. And my work is based on using lots of genome sequence data, complicated mathematical models and computing to try and understand what happened in the past and how we got where we are today.

Will - What is it about genetics that really excites you? Why did you choose to walk this path?

Aylwyn - Well, interestingly enough, I initially didn't. I was trained as a physicist, so this is a field I came into somewhat later on. It's actually not so uncommon in the field that I work in because it's quite mathematical and the training that you get in physics is relevant for it. But I think something I've always been interested in because genetics is such a fundamental part of understanding what we are and what was the journey that we all went on to get here. So I think in order to understand that you have to understand genetics.

Will - And last but not least…

Shivani - I'm Shivani. I'm a final year medical student at Cambridge. My interest is primarily in oncology, clinical oncology. I did my bachelor's in genetics three years ago. Now, my interest in genetics comes from interest in science and understanding who we are. Why are we more likely to get certain diseases, what can we do about that? And obviously oncology is where it all comes together and we go deeper into the genes and why did things change, what can we do to prevent it and treat it?

Will - Far be it for me to drive a wedge, but why is clinical so much better than <laugh> evolutionary?

Shivani - I think with clinical it's applied. So we're living in the UK which is obviously an aging population and there's so many advances with genetics as well. So you can take a finding, you can apply it to human health and you can actually see an outcome in terms of people living longer and better quality of lives. And that's sort of why I chose medicine in the first place as opposed to pure science.

Will - Very noble. Any thoughts?

Aylwyn - No, absolutely. I can see that it's probably what drives a lot of people's interest in genetics actually, is that desire to kind of use it to have a real impact on people's lives and health. And often you meet biologists who are driven by surprising different motives, someone to understand how things work today in animals and other organisms and other people want to understand how it came to be. And it's quite interesting how those two questions are quite different and involve different ways of thinking about the same problems.

Will - I hope we are all united by an insatiable curiosity. Well let us jump straight into the news then. I think first up having just come off the back of a delightful lunch, we have the story that a new Northwestern University medicine study has found that a person's genetic makeup plays a role in determining whether they can stick to a strict vegetarian diet. Now Shivani, before we get into genetics, why do you think a study into vegetarianism is so pertinent now?

Shivani - That's a very relevant question. I think one should always ask, what impact does this have on society, on people? There's a couple of reasons I believe so one is the environment. Obviously thinking about climate change, we know that methane produced by raising cattle and beef is a large percent, I think at least 20% of greenhouse gases. There's obviously ethics. People are not happy with how cattle and other animals are being raised. There's a question of health. So red meat's been linked to colon cancer and I think people are generally more aware about what's in their food, what percentage of saturated versus unsaturated fats. So there's probably quite a lot of factors driving towards a more vegetarian based diet.

Will - When a study like this comes out, when it says there's a genetic disposition, when you're looking at something like that and there's X amount of genes are dictating whether or not you have a predisposition towards vegetarianism is. What does that mean?

Shivani - So that's a very fair question and before I read these sort of articles it's something that I asked too. So speaking directly about this is quite interesting. So the genes themselves affect two main things, metabolism and taste and the interplay between metabolism, taste and preference towards a certain diet are genetically controlled. So that's where that comes in.

Will - That sounds like a lot of things to factor in when talking about genetic disposition. Is it a lot of genes that they've looked at that account for this?

Shivani - A total of 11

Will - Is that a lot <laugh>? That doesn't sound like a lot.

Shivani - So the thing with GWAS studies is I think as we were speaking over lunch there's a lot to do with maths and kind of saying is this statistically significant versus is it not? And you have to be careful when drawing a conclusion when things are associated versus to 100% say this causes that. And that will probably never be the case because genes and environment there's a lot of interplay. So we can say there's an association that has been found.

Will - Hmm. So you're saying that people who have a gene that makes vegetables taste better <laugh>?

Shivani - Well there are definitely genes that control metabolism. Your metabolism then controls how you taste certain things and then that controls your preferences. So it's more of a network of very complex factors.

Will - You touched on it briefly for a second there, but there's also this huge environmental thing, upbringing, what you have access to eating as well in terms of this genetic predisposition. Does it have an equal weight? What's the ratio between environmental and genetic in this instance?

Shivani - So I'll give the example of coffee so people who metabolise coffee quicker find that the taste is better and will therefore consume more coffee. That's been shown in the previous study. Now if that person who enjoys coffee is living in a society where there's not a lot of coffee consumption versus if you're living somewhere in South America where it's a staple part of your diet, I think that would definitely influence how often you are consuming coffee.

Will - So I hate coffee so does that mean I can't metabolise it properly?

Shivani - Perhaps that could be a problem with your gene <laugh>. Yes.

Will - Coming back to the whole 'why is this relevant?' meat alternatives are better for the planet that's provable in terms of emissions but aren't necessarily currently better for the person eating them. This study therefore is presumably useful for those seeking meat-free alternatives.

Shivani - I think that really varies. So in terms of plant-based foods, it depends on how it's processed, it depends on how much salts are added. Preservative plants definitely have a better unsaturated to saturated fat ratio than animal meats and red meats have. And in terms of this kind of vegetarian thing is actually to do with fatty acid metabolism and the type of fatty acids which are complex sphingolipids found in meats have been linked with certain neurodegenerative diseases such as Alzheimer's, autism, et cetera. So again, it's one thing to say this causes this, it's another to say there's an association, but there's definitely a role in terms of the types of lipids found in meats versus vegetables and how is that prepared?

Will - Are either of you vegetarian?

Aylwyn -
Not me, no. Although increasingly these days thanks to my daughter being vegetarian, that's sort of had an impact on all our diets at home. There's a lot of stories like this and we're probably going to talk about quite a few of them and I think the context for all of any study like this is just how complicated the biology of any given trait is. And particularly something like this, which is a behavioural trait, human beings are complicated enough just in their physiology and their biology in that sense. But then when you add into things that are going on in their brains that make them do one thing rather than another, it suddenly becomes almost impossibly complicated to imagine how does one study this? And traditionally in science we approach things from the perspective of, you know, trying to put together a causal chain of this causes that, this causes that, and we end up with this outcome here and now we understand this phenomenon. And, Those, you might call that sort of an understanding of mechanism. But it's just too complicated. And so instead we do these association studies, which is really just a statistical correlation, but as soon as you've done that, the complexities don't go away, they're all still in there. So the people who you've identified as being more likely to be vegetarian or drink coffee or whatever, there's a whole bunch of factors in their culture and how that impacts their diet and the environment that they live in and all kinds of other things that you can think of. Every single one of those is potentially going to be a factor and trying to tease those things apart is very difficult.

Will - The more you read into it, it seems from an outside perspective, the sheer nebulous nature of genes, even in just one human being means that, how could you possibly tell that a certain amount can lead to a concrete evidence that you are more or less likely to be predisposed to anything?

Aylwyn - Yeah, I mean there are a few cases, rare cases where we have the typical example of Mendelian diseases where, if you have this particular genetic variant then you will have the disease. Most traits do not behave like that. It'll be lots of tiny little effects from all over the genome. You know, one gene maybe has an effect on a protein which is involved in some kind of minor way and another one will do something else to some other protein somewhere else. And after a huge complicated interaction of all these things, there'll be some sort of 5%, 10% effect on the trait. You know, that's what we're trying to deal with. So most things we're trying, we're teasing apart these tiny effects and trying to look at them in aggregate and maybe if you have a large enough number of people they start to become clear.

Will - And are you a vegetarian <laugh>?

Shivani - No. But definitely something to consider.

Will - Having said all of that, we must now turn to a study which is probably going to make us all tear our hair out again. We've already been through enough pain. However, a study out of the French National Institute for Agriculture Food and Environment has concluded that having certain Neanderthal genes can raise your sensitivity to pain. But I guess before we get into that, how on earth do you measure or quantify pain to begin with?

Aylwyn - I'm fairly sure it involves inflicting pain on people in rooms and seeing when they say 'ow' or some equivalent, you know, that's, I think, the nature of it. It's one of those physiological responses that people have devised. I'd say the ethics are probably quite unpleasant to try and get through the experiment.

Will - I saw the methodology of that paper and it's extraordinary because it involves rubbing mustard oil onto people's arms until it burns. But I guess the question is, which, if we could even put a location on it, which genes would code for pain reception?

Aylwyn - Well, I know that there's a couple of genes that people have identified and I think the interesting thing about it to my mind is that different types of pain seem to have different genetic mechanisms that are involved or that have been associated with them. So pain due to temperature has a different physiological, potentially genetic, mechanism from pain due to pinpricks in the skin or insults to the body in that way. So I think that the actual details of it, in most cases are going to involve genes that are involved with signalling because pain is one of these signals that goes through the body and therefore cell signalling mechanisms like channels that are there in the cell membranes that let ions through. That's kind of how cells communicate with each other in the body. Those kinds of genes, I think, are typically what's implicated in these mechanisms. But again, those are the ones that we've seen so far. These are going to be complicated, probably not going to be a very simple thing. And the ones that we've seen, I think we know them because something's gone wrong and the person with some unfortunate person with this variant has a hypersensitivity to pain or equally bad and no sensitivity to pain. You know, both of those are bad conditions to have.

Will - It's interesting that you say that there's different areas for different kinds of pain because I think there might be studies that say the sort of people who are less sensitive to pressure based pains are more sensitive to use say temperature based pains. So there could be some kind of even evolutionary trade off between the amount of the types of pain you would have to endure. Say your ancestors walked a lot in the cold but didn't have to carry a lot, so maybe you don't need as much pressure pain, but they do need more temperature pain. I don't know if there's anything in your mind.

Aylwyn - Well, it's a good example of when you're trying to address evolutionary questions. I mean we've been talking about how hard it's to come up with explanations for just how the body works today, trying to come up with explanations for how something might have evolved is if anything even harder. And there is a tendency, it's actually quite easy to come up with stories sometimes, many of which are very plausible. I mean the one you've said is quite plausible, but how on Earth would go about actually establishing that that was how it evolved? Sometimes there are signals that we can see, and particularly with ancient DNA sometimes we can see that yes, actually in the past this gene was more prevalent and this one hasn't, or this variant I should say. But by and large we have to be pretty careful about leaping to a story about why something may have happened or whether or not there was a trade off. It's kind of opening up another whole can of worms. I think that the interest for me in this particular story actually was not so much about, you know, what does it tell us about pain? I don't know if it does, but the context being the prevalence of Neanderthal allele variants in everybody's genome are nearly everyone's genome. So they're in a few percent of people's genomes outside of Africa. People with African ancestry have a lot fewer or known Neanderthal ancestry in their genome. And there's been a lot of studies in the last decade or so about this and this was an interesting example of how people are very keen to find meaningful impacts of Neanderthal ancestry in us. You know, it's not enough just to say, 'well this is what's happened in the past and this interesting event,' but it also affects, it also makes us more or less likely to have some kind of condition. So there's some sort of deep requirement for us to be able to explain things in those terms.

Will - Exactly on point. There was a study a few months ago, maybe a year ago, that having a certain amount of Neanderthal DNA in you meant you were more susceptible to COVID and long COVID.

Aylwyn - Yeah. And there's been a bunch of others. A related study looking at cold adaptation in various people. There's been effects that have been injected about effects on diabetes. I mean there is some interesting genetics behind this, some interesting evolutionary genetics about the, that what you would expect to happen when a population like Neandertals who have been in a different environment and maybe in quite a small population size, what happens when their genes come into a much larger population, which is what we think happened about 50 to a hundred thousand years ago. And we expect actually by and large there to be those kinds of variants to not do very well in the new population and to be responsible for deleterious effects, you know, things that generally have a bad impact. Every now and then, there might be a few good things that help you adapt to environments, but that's the actual expectation here. And so it's totally plausible that they are having some, you know, they're involved in maybe certain diseases and things, but again, it's quite hard to establish it with certainty. So one has to be a little bit careful about some of these things. Because the numbers are often quite small in some of these studies.

Will - We set this up as explaining the news segment, but now it's let's trash the news. It's all impossible to say.

Aylwyn - I think that's where we're going, right.