Research may help develop new ways to diagnose and treat communication disorders

A genomic achievement that's for the birds -- and for humans

An international research consortium has identified more than 800 genes that appear to play a role in the male zebra finch's ability to learn elaborate songs from his father. The researchers also found evidence that song behavior engages complex gene regulatory networks within the brain of the songbird- networks that rely on parts of the genome once considered junk.

The zebra finch genome sequence and analysis published in the April 1 issue of the journal Nature was funded in part by the National Human Genome Research Institute, a component of the National Institutes of Health.

"By comparing the finch genome with the human genome, we should now be able to expand our understanding of learned vocalization in humans. Such information may help researchers who are striving to develop new ways to diagnose and treat communication disorders, such as stuttering and autism," said NHGRI Director Eric D. Green, M.D., Ph.D.

The zebra finch (Taeniopygia guttata), which derives its name from the black-and-white stripes on the male finch's throat, serves as a valuable model for studying human speech, communication and neurological disorders. The finch is the first songbird - and the second bird, after the chicken - to have its genome sequenced.

A major reason researchers decided to study the zebra finch genome was the male bird's ability to learn complex songs from his father. At first, a fledgling finch makes seemingly random sounds, much like the babble of human babies. With practice, the young bird eventually learns to imitate his father's song. Once the bird has mastered the family song, he will sing it for the rest of his life and pass it on to the next generation.

This ability to communicate through learned vocalization is lacking in chickens and female zebra finches. Though female finches do perceive and remember songs, researchers suggest that their inability to learn songs may be due to differences in sex hormones, as well as chromosomal sex differences affecting the brain. In addition to male songbirds, other animals that communicate through learned vocalizations include other songbirds, parrots, hummingbirds, bats, whales and humans.

The chicken and zebra finch genomes are similar in many ways. Both have about 1 billion DNA base pairs - roughly one-third the size of a human genome. However, researchers discovered that some genes associated with vocal behavior have undergone accelerated evolution in the finch. For example, they found a disproportionately high number of ion channel genes among the 49 genes in the finch genome that are suppressed, or turned off, in response to song. Ion channels allow the movement of ions (electrically charged particles) across cell membranes. Human ion channel genes have been shown to play key roles in many aspects of behavior, neurological function and disease. Consequently, the researchers suspect that the evolution of this group of genes in songbirds may be essential for learned vocalization.

The consortium, led by Richard K. Wilson, Ph.D., director of the Genome Center at Washington University School of Medicine in St. Louis, also identified portions of the genome crucial to regulating the activity of genes involved in song behavior. While many parts of the genome are engaged during vocal communication, one surprising finding was the extensive involvement of non-protein coding ribonucleic acids (ncRNAs).

Protein-coding components make up just a small fraction of the genomes of humans and other animals. It was once thought that the non-coding part of the genome was not essential, amounting to biological junk. Recently, researchers have begun to amass evidence that many parts of the non-coding regions serve important biological functions. Analysis of the zebra finch genome sequence suggested that ncRNAs, which have been proposed to contribute to the evolution of greater complexity in humans and other animals, may be a driving force behind learned vocal communication.

"These findings will transform scientific research on the songbird system," said Story Landis, Ph.D., director of the National Institute of Neurological Disorders and Stroke (NINDS), which also provided support for the study. "Although scientists understand much about how songbirds acquire and modify their vocal patterns, the availability of the genome sequence will allow insight into the molecular underpinnings of this natural behavior. This could lead to better understanding of learning and memory, neural development and adaptation, and speech and hearing disorders."

Source: NIH/National Human Genome Research Institute