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International Team Sequences Songbird Genome

By Andrea Anderson

NEW YORK (GenomeWeb News) – An international research team reported online in Nature today that they have sequenced the genome of the zebra finch, Taeniopygia guttata, a songbird used as a model organism in studies of the neuroscience involved in vocal learning and vocal communication.

The team used Sanger sequencing to tackle the zebra finch genome — only the second bird genome sequenced so far. They then compared the genome with that of the chicken and assessed transcription and small RNA patterns in the zebra finch brain following exposure to song.

"The goal, really, was to generate the assembly so we had a template to look at these genes that are regulated in the brain," lead author Wesley Warren, a genetics researcher at Washington University's Genome Center, told GenomeWeb Daily News, explaining that the zebra finch genome holds clues to the bird's biology as well as the evolution and regulation of vocal learning and communication in other animals.

Songbirds learn to sing by imitating older birds. Past research suggests a forebrain region called the song control nuclei mediates singing and song recognition. And birds' brains seem to change dramatically when male birds learn to sing as juveniles, Warren and his co-authors noted. Even so, much remains unknown about the genetics behind such processes.

"The act of singing induces gene expression in the male song control nuclei, and these patterns of gene activation also vary with the context of the experience," the team explained. "The function of this changing genomic activity is not yet understood, but it may support or suppress learning and help integrate information over periods of hours to days."

Because female zebra finches don't sing, the researchers focused on a male bird for the current study, using the Sanger approach to sequence the bird's 1.2 billion base genome to about six times coverage.

They also used the Illumina Genome Analyzer II to sequence complementary DNAs from the forebrain region of 50 juvenile and 850 adult birds in an effort to look at differences that occur in the brain as zebra finches age.

Based on their analysis of the genome, the team estimates that it contains around 17,475 protein-coding genes. Of these, 9,872 genes appear to be expressed in juvenile birds' forebrains, while 10,106 are expressed in adult birds' brains.

Next, the researchers compared genome sequences and chromosomal patterns for the zebra finch with the genome of the chicken, which belongs to a lineage that diverged from the zebra finch lineage roughly 100 million years ago. In so doing, they were able to start teasing apart genomic patterns found across birds species from those that may be involved in vocal communication.

For example, while zebra finch genome alignment to the chicken genome did not yield many structural surprises, Warren explained, the team did detect differences in the repeat content of the two genomes. In particular, the zebra finch housed three times as many long terminal repeat elements and contained short interspersed repeats that were absent from the chicken genome.

But both the chicken and zebra finch genomes lacked some genes found in mammals, including those coding for teeth, mammary glands, and a neuronal protein called synapsin 1. The songbird genome also contained expansion in some gene families compared with sequenced mammalian genomes.

Meanwhile, the team's expression analyses suggest that singing affects the levels of at least 807 genes in the song control nuclei of the zebra finch brain.

They also found evidence that a large set of non-coding RNAs contribute to vocal learning. For example, the expression of some non-coding RNAs, including a conserved miRNA called miR-124, are curbed when birds hear new songs, highlighting the intricate genetic processes involved in zebra finch communication.

"Now we know that there's this huge complexity that is very rapidly stimulated in the process of hearing song," Warren said.

In an effort to more fully understand which genes are involved in the neurobiology behind vocal communication in the zebra finch, the team also looked at the overlap between genes whose expression changes in the forebrain when birds hear songs and genes that appear to be under positive selection in the genome.

Based on such experiments, the researchers believe "the experience of singing and hearing song engages complex gene regulatory networks in the forebrain, altering the expression of microRNAs, transcription factor genes, and their targets, as well as of non-coding RNA elements that may integrate transcriptional and post-transcriptional control systems."

In the future, the researchers plan to use findings from their zebra finch results to try to better characterize vocal learning pathways in other animals, including humans.

"By comparing the finch genome with the human genome, we should now be able to expand our understanding of learned vocalization in humans," National Human Genome Research Institute Director Eric Green, who was not involved in the zebra finch sequencing study, said in a statement. "Such information may help researchers who are striving to develop new ways to diagnose and treat communication disorders, such as stuttering and autism."

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