Regulation rules

04 November 2014

Interview with

Lionel Christiaen, New York University

If two animals look the same, you might expect that they have similar genes being regulated the same way, however this is not the case, according to Lionel Christiaen of New York University, who has been looking at different species of sea squirts...

Lionel - My lab studies the development of marine organisms called sea squirts and the reason why we study these animals is because they have very few cells that they use to make their heart. So we can study these by looking at every single cell. And we study the genes which are activated in the cells and eventually tell the cells what to do. So in this particular study, we were wondering about how the mechanisms that control the development of the heart are conserved between very distantly related species. Because their embryos are almost identical to, every cell is organized and different tissues organized in very similar ways. But these animals have diverged more than 500 million years ago but they look identical as embryos. And so we were wondering what are the underlying genetic mechanisms that allow this conservation to have the same organization even though the genetic material is completely different.

Chris - So are they using the same genes and controlling them differently or are they using the same control mechanisms but different genes in order to arrive at this very similar outcome?

Lionel - Okay. So this is a very good question.  We found that to make the heart, they used the same genes at about the same time in the same cells. Okay? So the gene activation patterns remain the same in spite of this great evolutionary distance. What we found is that the mechanisms that control these activities are now the ones that have changed a lot.

Chris - Does that mean that if you were to take the control mechanism from one species and put them into the other species, they just wouldn't work despite the fact that the genes are pretty much the same?

Lionel - Yes, exactly. In other words one species cannot read the genetic code of the other species and vice-versa even though their own genetic code has evolved to maintain the output the same.

Chris - Why do think this has happened?

Lionel - Our favourite hypothesis is that every gene is activated by a small group, maybe about five, of proteins called regulators and each regulator can activate many different genes. Not all the genes but many different genes and we think that the cells, they may contain up to 50 regulators. So one way to change in evolution is that if the same gene, instead of being activated by the same five regulators every time, draws five different regulators from the pool of 50 which are available such that the gene would still be activated as time goes by and species change but the exact five regulators that control it may change.

Chris - Why would that be a beneficial strategy for the organism to adopt?

Lionel - I can only speculate but I would argue that this mechanism would buffer against dramatic changes that would end up being lethal. It is not clear that this would be an advantage. What is clear is that it happens and so you may take it from the angle of it happened because it can happen because the cells have the potential to change the underlying mechanism and yet keep the outcome the same.

Chris - So what do you think are the implications of this particular finding are because now, obviously, we have a lot more insights thanks to your work into how this particular sub-group of organisms develop and how evolutionary time has affected the way they control their genes. But what are the broader implications here?

Lionel - One of them is what do model systems mean because for example here we have two species. If we look at the way they develop and gene activity, they look the same. And so we could have focused on describing the mechanisms to regulate gene activity in one species and eventually assume that those mechanisms were going to be the same in the other species because the input and the output are very much the same. But we found this rearrangement of the underlying mechanisms which now suggests that mother species made for biomedical research for example may point to a direction and some of the mechanisms are likely to be conserved in humans for example or in other modern organisms. But then the underlying  relationships between the parts may have been rearranged a little bit.

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