Small RNAs Mean Big Complexity

Vertebrate Complexity Arose at the Same Time as the Number of MicroRNA Families Increased

by Dr. Barry Starr, Stanford University

February 22, 2008

Most biologists agree that vertebrates are more complex than invertebrates. A monkey is more complex than a sponge. And a human is more complex than a worm.

A new study suggests that the reason for this difference in complexity is tiny RNAs called microRNAs. The study found that right about when vertebrates split off from other animals, there was an explosion of these microRNAs in their DNA.

This makes sense since most scientists think that complexity comes from how genes are controlled and not the genes themselves. They came to this conclusion right after they sequenced the human genome and compared it to other animals.

When scientists figured out all 3 billion letters of human DNA, they were surprised at how few genes there were. There weren't that many more than a fruit fly. Or a simple worm called C. elegans.

This meant that complexity didn't come from the number of genes an animal has. (Or that people and worms were equally complex which no one wants to believe.) So scientists came up with a new theory—complexity comes from how similar genes are used. And this is where microRNAs come in because they affect how an animal (or plant) uses its genes.

MicroRNAs Control How Genes are Used

MicroRNAs control how genes are used
by controlling how much mRNA
gets translated.

Until a few years ago, microRNAs weren't that well studied. In fact, scientists didn't even know they were there.

Now scientists are finding them everywhere. And finding out how important they are.

Scientists have found that they are important in diseases like cancer as well as in heart and immune function. They are also critical in determining what kind of cell a stem cell will become. And they have lots of other functions too, only some of which we know about.

MicroRNAs accomplish all of this because they can regulate how specific genes work. To understand how, we need to dig a bit deeper into some basic biology.

In a cell, there are three critical molecules involved with genes. These are DNA, RNA, and proteins.

DNA has the instructions for making and running an organism. It is the central brain of the cell.

Some of DNA's instructions are found in genes. Each gene has the instructions for a specific protein that does a specific job in the body. Proteins carry our oxygen, help us digest our food, let us see and think, etc. They pretty much do all of the work in a cell.

The cell doesn't go directly from the instructions in DNA to protein though. First a cell copies (or transcribes) the instructions in the DNA into RNA. This messenger RNA (mRNA) is then translated into protein.

Besides genes, DNA also has the instructions for when and where to turn on a gene. And how much to turn it on. These instructions come in many forms one of which is microRNAs.

MicroRNAs are RNAs that are not turned into protein. Instead, they control how much protein gets made from an mRNA. They do this in two different ways.

One way is by destroying a gene's mRNA. Let's say a gene's instructions are read and an mRNA gets made. On the way to getting translated, a microRNA can come along and destroy the mRNA. No mRNA, no protein.

The second way a microRNA can control how much of a protein gets made is by mucking with translation. If the cell can't translate the mRNA, then no protein gets made.

In both cases a gene gets turned down. Or even turned off.

This wouldn't necessarily be all that useful if microRNAs turned down all genes. Luckily, microRNAs are specific for certain genes. (Click here to see where that specificity comes from.)

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Evidence that Vertebrate Complexity Comes from MicroRNAs

Vertebrates gained 41 microRNA
families right about when they split
from other animals.

So how did scientists figure out that vertebrate complexity happened around the same time as an explosion in new microRNAs? By comparing the DNA of lots of different animals.

MicroRNAs are ideal for these kinds of studies for three reasons:

1) New microRNAs are added to an organism's DNA frequently
2) Once there, microRNAs do not mutate very much at all
3) Once there, microRNAs are not lost

What this means is that as DNAs change through history, microRNA changes are easy to see. The researchers know a lot about the microRNAs found in various vertebrates. So they asked, how far back do you need to go to find animals that lack most of these microRNAs.

What the researchers found was that there were two periods where there was a dramatic increase in the number of microRNAs. One was when vertebrates split off from a common ancestor. And the other was when eutherian or placental mammals split off. (Most mammals around today are placental.)

For example, vertebrates have 41 more microRNA families than the animals they split off from. And eutherian mammals have 63 more microRNA families.

Of these two, only the vertebrate change is probably significant. This is because the increase in microRNA families happened over a much shorter time with the vertebrates. The rate of new family addition was 3-10 times higher for the vertebrate transition compared to the eutherian mammalian transition.

It is important to note that the scientists don't know a lot about the microRNAs of a lot of these other animals. They know that the complexity of vertebrates happened at the same time that a large number of new microRNA families appeared. They do not know if the other animals have lots of microRNAs of their own. Or when they acquired theirs.

They also don't know for sure if the extra microRNAs led to the complexity or vice versa. Or if they just both happened by coincidence.

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Understanding Evolution

Content provided by the Department of Genetics, Stanford University.