How could microRNA have evolved to have such similar structure and function in plants and animals after evolving independently? You must be thinking, “What are the odds?!”

If evolution boiled down to nothing but random chance, the odds seem staggering indeed. No, I’m not about to say God guided evolution. What happens is there are certain traits about the system that constrain it to act in a certain way, making similar outcomes more likely.

To understand more fully, I have to teach you a little bit about microRNA biogenesis. Awww yeeeaaah!

Adapted from Berezikov 2011

In animals, a microRNA gene is transcribed to make what’s called “primary microRNA.” This pri-microRNA forms a hairpin structure – that is, it folds over and complementarily base-pairs to itself, forming a step and loop. This pri-microRNA is trimmed by the protein Drosha and is then shipped out of the nucleus as an ~80 nucleotide precursor microRNA. In the cytoplasm, the protein Dicer cleaves the pre-microRNA to form the mature ~22 nucleotide microRNA, which will go on to be involved in gene regulation.

In plants, pri-microRNA still forms hairpins, but their size can be far more variable. Plants also lack Drosha – all of the processing is done by a Dicer homologue.

You’re probably thinking, “So they’re processed differently. This doesn’t really convince me of the odds.” But what’s important to notice is that both of these systems share a couple of key things, which make convergent evolution more likely:

1. Both use the protein Dicer to process mature microRNA. This is thought to be an exaptation – where a trait initially evolved to have one function, but has subsequently come to have another. Dicer is thought to initially be used to cleave foreign RNA particles, for example from viruses. There’s also evidence that suggests Dicer plays a role in repairing double stranded breaks in DNA. Since Dicer was already present in plants and animals because of these more ancestral functions, it was available in both lineages to be used for something else. Plants and animals didn’t have to evolve a totally new protein to process microRNA – they used the machinery they already had sitting around.
2. Both process microRNA from hairpins. RNA hairpins spontaneously occur all the time, and some of these spontaneous hairpins give rise to new microRNA. That’s because if a hairpin happens to process into a mature microRNA that conveys a fitness advantage to an organism, natural selection will act to perpetuate it. If a hairpin results in an unfavorable outcome like disease, purifying selection will purge it from the population. Because RNA hairpins spontaneously occur and Dicer was already around, natural selection would act favorably on a system where processing hairpins leads to a fitness benefit.

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Since my research focuses on primates, I don’t exactly work with plant microRNAs. But they’re still fascinating enough that I wanted to touch on them. Plant and animal microRNAs are very similar – they’re approximately 22 nucleotides in length, they’re processed from larger hairpin structures, and they function by downregulating messenger RNA. But they have a number of differences because microRNA in plants and animals evolved independently.

Yes, this similar system arose separately in the plant and animal kingdoms. No, this is not proof for God. This is an example of convergent evolution, where the same trait is acquired independently in different lineages. Think of the ability to fly in insects, birds, and bats. The evolution of microRNA is the same, it’s just more molecular instead of having an obvious effect like flight, which is visible to the naked eye.

Why do we think plant and animal microRNA evolved independently? One major piece of evidence is that there are no homologous microRNAs between plants and animals (homologous meaning shared through a common ancestor). This is especially striking when you compare it to microRNAs within animals, a number of which are homologous. There are some animal microRNAs present throughout the whole animal kingdom, from sponge to fruit fly to orangutan, that just don’t exist in plants. Plants have their own set.

Another thing supporting independent evolution is that plants and animals have different processes for generating mature microRNA. In plants, microRNA is fully matured in the nucleus before being shipped out to the cytoplasm for use. In animals, much of the processing takes place out in the cytoplasm. Animals have additional proteins that are involved in processing – I’ll touch on it a little more in my next post. Also, plant and animal microRNA differs in how it targets messenger RNA. In plants, the whole ~22 nucleotide microRNA is involved in complementary base-pairing with the messenger RNA. In animals, only a 7 nucleotide “seed region” of the ~22 nucleotide mature sequence determines which messenger RNA it’s supposed to match up with.

A final piece of evidence is that microRNAs are missing in other forms of life. They’re absent in fungi, placozoans (the most basal animal lineage), and choanoflagellates (the closest living relative to animals). It’s more likely, especially considering the other evidence, that microRNA arose twice independently, rather than microRNA being lost multiple times in the specific lineages that happen to make it look like it arose twice independently. The latter would be getting into “Satan buried the dinosaur bones to make it look like a natural process” territory!

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Like I said previously, microRNA is typically highly conserved (have the same sequence) across animals because it’s involved in such important biological processes. But some microRNA isn’t conserved, which makes it particularly interesting. Is it not conserved because it just doesn’t have an important function? Is it not conserved because the divergent microRNA confers a specific fitness benefit to an organism? Or is it a rare mutation that leads to a disease like cancer?

That’s where my particular research comes in. I’m investigating microRNA variation within human populations and across the primate lineage. Here are some examples of interesting trends I may find:

1. A microRNA is totally conserved across primates and other animals. This microRNA is likely involved in a really important biological process, like making a type of tissue.
2. A microRNA is totally conserved within primates, but differs from other animals. This microRNA could confer some primate-specific trait.
3. A microRNA is totally conserved within humans, but differs from other primates. This could be an example of “what makes us human.”
4. A microRNA is not conserved at all. The more likely explanation is that this isn’t a functional microRNA at all. That’s the risk with working with such new data. Other types of small RNA can be erroneously labeled as a microRNA. MicroRNA is a specific class of small RNA because it’s processed in a very distinct manner and has a specific function.

This is post 7 of 49 of Blogathon. Donate to the Secular Student Alliance here.