The Singing Genome

Research team unravels genome of the zebra finch songbird.

Zebra finches have emerged as the primary animals used as a model to study vocal communication in humans, says David Clayton, an LAS professor of cell and developmental biology.
Zebra finches have emerged as the primary animals used as a model to study vocal communication in humans, says David Clayton, an LAS professor of cell and developmental biology.

David Clayton is not actually a bird watcher—a bird listener is more like it.

Back in 1992, this LAS researcher discovered that when a zebra finch songbird hears a new song from a male of the same species, it triggers a specific gene in the brain. This was one of the earliest discoveries showing that social interactions can turn genes on and off in the brain. Now, for the first time, the “singing genome” of the zebra finch has been mapped, thanks in part to the leadership of Clayton, a University of Illinois professor of cell and developmental biology.

Researchers chose to unravel the genetic code for zebra finches because these birds have emerged as the primary animals used as a model to study vocal communication in humans, Clayton says.

Half of the birds on earth are songbirds, so they are a highly successful group of animals, he points out. That’s why they have been used to study everything from the synthesis of hormones to sex differences in brains. Songbirds were even used in the breakthrough discovery in the 1980s that adults can create new neurons in their brains—destroying the long-held notion that it was impossible.

Of all songbirds, zebra finches make the best research models because they are very hardy and breed easily in captivity. In the U of I’s Beckman Institute, you can even find zebra finches outfitted with small, wired helmets, which allow researchers from the Department of Psychology to track brain patterns in the birds without harming them.

According to Clayton, the chicken was the first bird to have its genome sequenced; and at first it appeared that it was going to be the last one because of the hefty price tag. But with advances in genomics, costs have plummeted, so the National Human Genome Research Institute commissioned the zebra finch project in 2005. Clayton was one of four leaders on the zebra finch genome central steering committee, along with colleagues from Washington University, UCLA, and Sweden.

U of I neurogenomics research on zebra finches discovered that an enzyme, known primarily for its role in killing cells, also plays a part in memory formation. This research, by Clayton (above) and former U of I colleague Graham Huesmann, could have implications in the treatment of memory impairments such as dementia and Alzheimer’s disease.
U of I neurogenomics research on zebra finches discovered that an enzyme, known primarily for its role in killing cells, also plays a part in memory formation. This research, by Clayton (above) and former U of I colleague Graham Huesmann, could have implications in the treatment of memory impairments such as dementia and Alzheimer’s disease.

Clayton became interested in songbirds as a graduate student in the early 1980s, just when genomics began to take off. Prior to this period, he says, most of the work on songbirds revolved around field observations of their behavior. For instance, researchers learned that when a male zebra finch becomes an adolescent at about three months of age, he connects with an adult tutor to learn the one song that he will sing for the rest of his life. The song will be a copy of his tutor’s, but not a perfect copy.

Only the male zebra finch learns to sing, Clayton says, which makes the bird ideal for examining the differences in neural pathways between males and females. Therefore, as Clayton first became interested in the mysteries of the brain in the 1980s, zebra finches became prime lab models in the growing field of “neurogenomics.”

“Biological organisms like ourselves have two main control systems,” Clayton explains. “There’s the genome and there’s the brain, and traditionally people have studied them as two different things. Neurogenomics tries to understand how these two control systems talk to each other—how they interact.”

Most recently, U of I neurogenomics research on zebra finches discovered that an enzyme, known primarily for its role in killing cells, also plays a part in memory formation. This research, by Clayton and former U of I colleague Graham Huesmann, could have implications in the treatment of memory impairments such as dementia and Alzheimer’s disease.

Stephanie Ceman, another professor of cell and developmental biology, is also using zebra finches to look at the fragile X syndrome gene and its effect on vocal learning. In addition to cognitive impairment, fragile X syndrome causes defects in speech production, so zebra finches once again serve as ideal models for the study.

Mapping the zebra finch genome opens up the possibilities in such research projects, for the state of the art today is a far cry from when Clayton did his first breakthrough work on the songbird in 1992. Back then, he studied the expression of only one gene at a time, but today he can look at the interactions of 20,000 different genes in a single experiment.

“We’re no longer just scratching the surface,” he says.