Novel gene discovery in zebra finches

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 DESCRIPTION (provided by applicant): The availability of NIH/NHGRI-funded high quality genomes for non-human vertebrates, including avian species like the zebra finch and chicken, has made it possible to search for genomic features that are associated with traits whose mechanisms cannot be investigated in humans, thus requiring experimental model organisms. The study of some complex learned behaviors and their associated brain circuits illustrate well this point. We propose here a set of exploratory analyses in the zebra finch, a songbird, in order to elucidate the genomic basis of vocal learning, a complex behavioral trait that is a prerequisite for speech and language acquisition in humans. Zebra finches have emerged as the premier model organism for investigating the biological basis of vocal learning. In fact, no other organism, including rodents and non-human primates, provides a comparable experimental platform that allows investigators to relate neural and genomic features to a learned vocal behavior with close ties to human speech. Recent studies have revealed remarkable convergent molecular specializations in brain circuits for vocal control in songbirds and humans, pointing to a set of shared molecular requirements for birdsong and human speech learning. Such findings have broad implications for understanding genetic mechanisms that may underlie a variety of human communication impairments and disorders. Here we propose to implement a novel computational search algorithm that is designed to discover novel and duplicated genes in the genome of the zebra finch that are absent in a closely related vocal non-learning species (manakin), and thus possibly related to vocal learning. We anticipate that this exploratory effort will identify ~100 novel genes in zebra finches. To further test for a possible link to vocal learning, we will examine the occurrance of the identified genes in multiple other vocal learner birds whose genomes are now also available. An exploratory expression analysis will attempt to link the novel genes to specific brain cell types associated with vocal learning, as well as with other songbird traits of relevance to human health, including adult neurogenesis, brain dimorphisms and sex steroid action, and sleep modulation of learning. We will also explore whether expansions of functional protein domains in the novel genes are present in other avian vocal learner species, as well as in humans. If found in the latter, such features could potentiall be used in future studies of genetic correlates of speech proficiency and disorders. The outcomes will also guide future mechanistic studies to establish causal links between specific genes and vocal learning. Lastly, our intent is to implement a computational search algorithm of broad applicability that can be utilized for novel gene searches and genome curations in any target species of interest; such an algorithm should therefore be of broad use, particularly for analysis of recently assembled genomes that have low quality or no annotations.