What baboons can tell us
Individuals can vary because the genetic sequences they carry will be different. But variation can also occur, not just by changing the sequence of a gene but by altering its level of expression. As Jenny Tung, who's been looking at this question in wild baboons puts it, it's a bit like making two different cake recipes. Both are going to contain eggs, and milk, and flour. But if you alter the relative proportions of each, you get quite a different cake.
Jenny - It turns out that the protein coating sequence, so the ingredients in the cake as it were, are often very, very similar between different primate species or among different individuals within the same species. That suggests the amount of gene product that's being produced might be really important. And until recently, it was very hard to measure those values, at least on a genome wide scale. We knew that, theoretically, this should be important but we haven't been able to back that up with empirical data from real primates living in real populations until now.
Chris - What's changed that means that you can now do that?
Jenny - Well. There have been a lot of technical advances in really the last five to ten years that have meant you can measure whether genes are turned up or turned down in pretty much any species that you can get your hands on. Now we can actually look directly at the sequence products of the genes. And there's more of it if the gene is expressed a lot and there's less of that sequence product in the cells if the genes aren't expressed very much. You can also get a sense of how genetically different individuals are, and it's connecting those two things that we did in this paper to ask about whether genetic differences between individuals play a role in how many eggs go in that cake.
Chris - So, which species did you study?
Jenny - So, here we are studying Yellow Baboons. And the reason we did so is because we were able to take advantage of samples we collected from a really special population that I'm very fortunate to work with. It's a wild population of baboons in Kenya that's been studied since 1971. So, we actually know a lot about these animals, although we didn't know very much about their gene expression profiles until now.
Chris - And what did you take away from them to measure?
Jenny - So, these were blood samples. We just purify RNA from the cells and we're able to actually look at the DNA sequence that produced that RNA.
Chris - And you're using the RNA as an index of gene expression. The more RNA there is, the more gene products there is, and therefore, the more active that particular gene that produced that RNA molecule originally must be?
Jenny - That's exactly right. Yes. And because we're using actual sequence data, so we're actually looking at the sequence of the genes as a measure of how much the gene was expressed. We also kind of get information about genetic variation in that sequence for free.
Chris - You study a big group of animals, you do this, you get the RNA profiles from them. What did it tell you?
Jenny - One thing it told us is that genetic differences between individual baboons play a really important role in determining, whether, gene expression levels tend to be high or low. This is pretty consistent with what we know in humans. But it turned out that it was actually much easier to identify these kinds of genetic effects on gene expression levels in the baboons than it has been in humans so far, suggesting that baboons might in fact be more genetically variable than your average human population. Those genes in baboons were also likely to be related to genetic differences among individuals in humans. So, genetic effects on gene expression levels in baboons are, to some degree, similar to the sets of genes that show the same pattern in humans. And that was interesting and surprising because it suggests that some genes are kind of more free to vary than others. Natural selection makes some genes very constant in the way that they are expressed, whereas other genes are allowed to vary in populations more freely.
Chris - What sorts of things do these genes that are changing very rapidly in the baboons specify in the body? What jobs do they do and what jobs are they controlling?
Jenny - Some of those genes are involved in immune defence, again, suggesting that when you're job is to cope with exposure to pathogens, being able to have a lot of variation and being able to evolve very rapidly might be important. Other kinds of things that we see are variation in genes that would respond to other kinds of environmental stimuli. Things that help your body cope with the environmental changes that it faces day to day.
Chris - Have you got a handle on the role of epigenetics here? Because obviously you're looking at gene expression levels but have you any handle on the role that the epigenetic influence might be playing in what you're seeing or is that mixed in there and you can't tell?
Jenny - Based on the data set that we reported on here, we can't tell because we didn't do any direct measures of the epigenome. But it's very tempting to speculate that some of the, particularly, the long-term influences of social environment on gene expression might be mediated by aspects of the epigenome because some of those things are known to be stable over quite some time. It's actually a great question. It's something that we're looking at in my lab now.