Nature's little lyrical squeakers

Singing mice (scotinomys teguina) are not your average lab rats. Their fur is tawny brown instead of the common white albino strain; they hail from the tropical cloud forests in the mountains of Costa Rica; and, as their name hints, they use song to communicate.

University of Texas at Austin researcher Steven Phelps is examining these unconventional rodents to gain insights into the genes that contribute to the unique singing behavior - information that could help scientists understand and identify genes that affect language in humans.

Phelps uses next-generation sequencing to decipher how the gene FOXP2 interacts with DNA to regulate the function of other genes. The process involves reading tiny fragments of overlapping DNA so that the entire sequence can be deduced. It is a procedure that generates massive amounts of data that only the processing power of a high-performance computer can handle.

"You need TACC to do it," said Lauren O'Connell, a post-doctoral researcher in the Phelps lab, referring to the Texas Advanced Computing Center (TACC), which houses the high-performance computers the lab uses. "The more data you have, the more memory it requires, so we can only process a lot of the data on Lonestar's high memory nodes." Lonestar is one of the top 100 high-performance computers in the world.

Linking a mouse song gene to human speech disorders

The song of the singing mouse is a rapid-fire string of high-pitched chirps called ‘trills’ used mostly by males in dominance displays and to attract mates. Up to 20 chirps are squeaked out per second, sounding similar to birdsong to untrained ears.

"We can choose any number of traits to study but we try and choose traits that are not only interesting for their own sake but also have some biomedical relevance," said Phelps. "We take advantage of the unique property of the species."

Within the last year, Phelps’s research on the behavior of the mouse has appeared in the journals Hormones and Behavior,and Animal Behaviour.But, one of his newest research projects is looking deeper: examining the genetic components that influence song expression.

Center stage is a special gene called FOXP2. "FOXP2 is famous because it's the only gene that's been implicated in human speech disorders specifically," Phelps said.

Having at least one mutated copy of the gene has been associated with a host of language problems in humans, from difficulty understanding grammar, to an inability to make the precise mouth movements needed to speak a clear sentence.

The FOXP2 gene is remarkably similar among singing mice, lab mice, and humans according to Phelps. To find parts of the gene that may contribute to the singing mouse songs, Phelps is searching for sequences unique to the singing mouse and testing them for evidence of natural selection, which weeds out mutations with no likely observable effect from those that are likely to contribute to singing behavior.

Future applications

At the most basic level, Phelps's research is asking questions about the biology and behavior of an exotic rodent. But finding out more about the link between FOXP2 and the song of the singing mouse could bring a better understanding into how the gene may contribute to language deficits in people, especially those with autism, according to Phelps.

"When people do genome-wide association studies in humans the genetic variation tends to occur in huge blocks. If you get some DNA sequence that predicts a phenotype [set of an organism's observable characteristics resulting from interactions of its genotype with the environment], like risk for autism, it's very hard to know what aspect in this very long stretch of DNA is actually important for that," Phelps said.

By identifying the sequences of DNA that interact with FOXP2 and other associated genes that are most vital to gene function, researchers in the future might be able to narrow down the huge blocks where a causal sequence is located into smaller pieces. In other words, reducing the size of the metaphorical haystack to a size where finding the needle is a much simpler task.