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Dartmouth's Kevin Peterson Discusses miRNAs and Evolution

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Name: Kevin Peterson
Position: Associate professor, biological sciences, Dartmouth University
Background: Postdoc, California Institute of Technology — 1996-2000
PhD, geology, University of California, Los Angeles — 1996
BA, biology, Carroll College — 1989
 
At Dartmouth, Kevin Peterson combines molecular biology with paleontology to explore the origin and evolution of animals. This work, combined with a friendship with Dartmouth researcher and microRNA pioneer Victor Ambros, has led Peterson to believe that miRNAs play a significant role in the ongoing evolution of animals.
 
This month, he and his colleagues published a paper in the Journal of Experimental Zoology describing a set of 18 miRNAs found only in protostomes and deuterostomes, but not sponges or cnidarians. The findings indicate that the miRNAs may have been instrumental in the origins of organs and therefore contribute to the evolution of body plans.
 
This week, Peterson spoke with RNAi News about his work.
 
Let’s start with an overview of your lab and its research focus.
 
I’m a molecular paleobiologist, and my primary interest is the origin and early evolution of animals, specifically the Cambrian explosion, which was this remarkable event where basically all animals with preservable skeletons appeared essentially at the same time — starting about 530 million years ago. It’s been this huge problem — even Darwin discusses it in The Origin of Species as one of the major problems with his theory.
 
We’ve been attacking it from a molecular perspective, so I do molecular phylogeny, molecular clocks, [and] evo/devo sorts of things, and I work with a variety of marine invertebrates. We just kind of fell ass-backwards into microRNAs. I had no intention of thinking they would even be important or relevant for the Cambrian explosion, but now basically the whole lab is turning towards microRNAs for this problem.
 
When did you start looking at microRNAs and how did that come about?
 
It came about [in part] because Victor Ambros is here [at Dartmouth]. Victor and I talked a lot when I first got here as a new professor. [Then] the [Amy] Pasquinelli et al. paper came out on [the miRNA] let-7 [in Nature in 2000], which I had known about because I was at those NASA [Evolution and Development] meetings where all of that [research] originated and was discussed.
 
We were really keen on [the fact that in let-7] we had a marker for larval to adult transitions [in C. elegans]. I thought that [transition] was really important for the Cambrian explosion. I now know that is fundamentally wrong, but at the time I was thinking it was really important, and with let-7 here we had a marker that seemed to be relevant for marine invertebrates.
 
One of the interesting things is that there is a group of animals called rotifers that have long been thought to be neotenic larvae. I thought that one way you could actually test that — because we never had a way to test the idea — is to look at let-7, because adult rotifers should not express, or at least up-regulate, let-7 since [the animal] doesn’t go through a metamorphosis — it should act like a marine larvae. So I … started playing around with rotifers and, to make a long story short, the rotifer has let-7, [but] doesn’t really up-regulate it.
 
We didn’t do much with [the findings, but later] we started playing around with it again … and thought, ‘Why don’t we look at a few more microRNAs?’ Then I thought, ‘Why don’t we add a few more taxa?’ Gradually, this really interesting pattern started to emerge to the point where we completely forgot about rotifers — rotifers suddenly became totally irrelevant. [Ultimately] we found the pattern that was reported in the [Journal of Experimental Zoology] paper.
 
So we had no intention of looking at microRNAs for the Cambrian explosion, but suddenly after we had that pattern, it seems as if [they] could actually hold some of the real insights into what was going on then.
 
Could you talk about the paper and your thoughts now on the Cambrian explosion?
 
We found this remarkable pattern of microRNAs. [Also,] their sequences don’t change — they’re remarkably conserved … and everyone in the field knows this, it’s nothing new, although nobody knows why. It’s as if the people in the microRNA field are ignoring that — they’re focused on these 8-nucleotide seeds, but yet the whole sequence is conserved. So we’re missing something, it seems. We don’t understand why they’re all conserved. And once they’re gained in the genome, they’re not lost.
 
And, they’re continuously being added to the genome over time. That was the thing that was so remarkable — you can do a Drosophila species tree and you can do a metazoan phyla tree with the same sets of markers. Because they’re constantly being added to the genome, you can always do phylogeny at any level, which is just remarkable I think.
 
The other thing is the organ-specific [miRNAs] … we don’t detect in organ-less animals. They’re not in cnidarians, they’re not in acoel flatworms. They arise on the tree where you actually get organs. We wanted to make a statement of causality: The origin of complex animal body plans is actually due in part to the evolution of these microRNAs.
What we’ve learned from cnidarians, and now we’re learning from sponges, is that all the transcription factors and signaling molecules are basal for metazoans. So cnidarians have all of these genes for brains and eyes and hearts, but of course they don’t have any organs whatsoever. Why is that? They have all the mRNA complexity, and we want to make the argument that they don’t have the non-coding RNA complexity — and I’m not totally convinced that microRNAs are the end-all, be-all. There might be a whole series of evolutionarily important non-coding RNA molecules that we’re not aware of. So microRNAs might only be the tip of the iceberg, but that’s the only data we have.
 
What so surprised me … is that we were always taught that it’s the regulatory network, it’s the transcription factors that are important. And everything I had written up to this [Journal of Experimental Zoology] paper focused on Hox genes and the like. That’s what allows you to build an animal, but it doesn’t give you body plans, it doesn’t give you morphological complexity, it doesn’t give you multiple cell types. The correlation between microRNAs and the number of cell types that we put in our last figure [in the paper], I think, is really striking. I think it’s the first indication of causality in terms of how you actually get more and more cell types, which is a metric of morphological complexity … because it is the most quantitative, if you will, of how to measure complexity in an animal.
 
Where does all this put you now in terms of what you’re doing?
 
What we’re trying to do now is test the paper, basically. Out of necessity, we could only look at two lineages, arthropods and vertebrates, because that’s where the most amount of information is. What we don’t know is all of the unique microRNAs that every animal lineage has evolved.
 
If you look at a mollusk, it will have a bunch of mollusk-specific microRNAs. And then it will share some microRNAs with annelids, and those will share some microRNAs with nemertians or bryozoans, and none of those microRNAs will have ever been present in the arthropod lineage or vertebrate lineage because they’ve been evolving independently. The prediction is that, for example, microRNAs that are present in these lineages will be used to build phylum-specific features. What makes a mollusk a mollusk and an annelid an annelid is not the Hox genes that it has but the microRNAs that it has. So we’re building [miRNA] libraries from a variety of different animals and different life stages of different animals, and just trying to test the hypothesis that way.

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