Humans Have the Genes to Talk the Talk

Putting a Human FoxP2 Gene into a Mouse Changes How Mice Speak

by Denise Chen

June 11, 2009

Now that the human and chimp genomes are completely sequenced, scientists have started looking at the genetic details of what makes humans unique. One key study area is human speech.

An important gene for human speech is called FoxP2. A new study shows that a mouse changes its “speech” patterns when its FoxP2 gene is replaced with the human one.

These mice squeak at a different pitch. And, the regions of their brains involved in speech change…the cells there become more developed.

These results confirm that FoxP2 is a critical speech gene and give scientists some clues into how FoxP2 affects human speech. The next steps are to figure out the details of what FoxP2 is doing in people and what genes it works with to give humans the ability to speak.

FoxP2, a Gene We Can’t Live or Speak Without

Human speech is very
complicated.

Speaking is no easy task! Many organs are involved in human speech, such as the lips, tongue, vocal cords, lungs, and brain.

Not surprisingly, something this complicated needs many genes to help coordinate all the parts. This is because each gene is usually in charge of a specific task.

For example, one gene might be involved in molding the tongue for forming words. Another might be involved in synchronizing proper breathing. And others might be important for interpreting speech in the brain.

One major gene involved in human speech is called FoxP2. This gene is very similar in different animals. In fact, it is in the top 5% of the most similar genes shared between humans and mice.

Scientists found this gene when they figured out why some people had a hard time controlling the organs they use for human speech. They had trouble speaking because they had a bad copy of FoxP2.

Remember, we have two copies of each of our genes—one from mom and one from dad. So we have two copies of FoxP2 also.

To speak well, people need two working copies of this gene. Just one working copy causes an inability to speak well. No working copies causes death (at least in mice).

When one bad gene copy makes something stop working, geneticists call this “haploinsufficiency.” There are many human disorders and diseases that result from haploinsufficiency of certain genes. Some examples include CHARGE, Cri-du-chat, and Turner syndromes.

More Information

The Talking Mighty Mouse

Scientists created a
“humanized” mouse by
replacing a mouse
gene with a human one.

Scientists want to learn more about FoxP2’s specific role in human speech. One way to do this is by putting the human version into a different animal and observing what happens.

A natural choice for this kind of experiment might be chimpanzees. Chimpanzees and humans share 98% of their DNA and swapping FoxP2 genes with chimps would provide us with a lot of information about human speech. But this experiment is both difficult AND unethical. So scientists put the gene into mice instead.

Scientists have studied mice for more than 100 years. Mice have shed light into many human diseases and are well established as an animal model for human genetics.

The researchers “humanized” mice by replacing mouse FoxP2 with the human version of the gene. Compared to normal mice, the “humanized” ones behave pretty typically. They are healthy, mate, and live just as long. Overall, it seems like “humanized” mice do fine with the human version of FoxP2.

So what’s the difference between “humanized” and normal mice? There must be an explanation for why a mouse’s FoxP2 gene is the way it is.

The researchers performed very comprehensive physical exams on all the mice, using a set of over 300 individual criteria to figure out the differences. For the majority of these tests, there was no difference between “humanized” and “mice” mice. But researchers noticed a few differences.

First off, details of their brains changed. And secondly, they squeaked at a different pitch.

Brain and Voice Changes

Researchers used a microscope and saw that some neurons were much more developed in a “humanized” mouse’s brain than in its natural cousin’s. They saw these neurons in a part of the mouse brain that deals with vocalization.

Neurons are
cells in
your brain.

Neurons are nerve cells that carry messages throughout our bodies. They look like trees and have branches, a trunk, and roots. The “humanized” mouse’s neurons had much more pronounced roots than a normal mouse’s neurons.

Trees take up nutrients with their roots and carry these nutrients through the trunk and into the branches. Neurons function in a similar way, taking messages in from their roots and shooting them out from their branches.

These “humanized” mouse neurons had longer roots and were found in a region of the brain called the basal ganglia that is used for language. Just like longer tree roots help trees absorb the nutrients they need, we can imagine that neurons with longer roots are more aware of messages in their surroundings. These neurons are also better at collecting and delivering messages.

Then, researchers recorded and measured the ultrasonic squeaks that the mice pups made when separated from their nests. These calls for help (and just mice squeaks in general) can’t be heard by the human ear.

“Humanized” mice squeak as much and as long as their natural cousins, but “humanized” mice have lower pitched squeaks. Having the human version of FoxP2 affects the way mice sound.

These results suggest that the human version of FoxP2 made small tweaks to “humanized” mice brains in areas that are related to speech. Since there are so many organs and genes involved in human language, we can’t expect mice to start talking the way we do by just giving them the human version of this gene. But this is definitely a first step.

What’s Next?

The next step is to look closer at the specifics of how FoxP2 makes these small tweaks in “humanized” mice. Also, we need to look at how FoxP2 interacts with the other genes that are involved in language and how these genes coordinate all of our speech organs. So stay tuned, and until then, chat away about the wonders of human language!

Denise Chen

More Information

Content provided by the Department of Genetics, Stanford University.