Abstract
Learning of most motor skills is constrained in a species-specific manner. However, the proximate mechanisms underlying species-specific learned behaviors remain poorly understood. Songbirds acquire species-specific songs through learning, which is hypothesized to depend on species-specific patterns of gene expression in functionally specialized brain regions for vocal learning and production, called song nuclei. Here, we leveraged two closely related songbird species, zebra finch, owl finch, and their interspecific first-generation (F1) hybrids, to relate transcriptional regulatory divergence between species with the production of species-specific songs. We quantified genome-wide gene expression in both species and compared this with allele-specific expression in F1 hybrids to identify genes whose expression in song nuclei is regulated by species divergence in either cis- or trans-regulation. We found that divergence in transcriptional regulation altered the expression of approximately 10% of total transcribed genes and was linked to differential gene expression between the two species. Furthermore, trans-regulatory changes were more prevalent than cis-regulatory and were associated with synaptic formation and transmission in song nucleus RA, the avian analog of the mammalian laryngeal motor cortex. We identified brain-derived neurotrophic factor (BDNF) as an upstream mediator of trans-regulated genes in RA, with a significant correlation between individual variation in BDNF expression level and species-specific song phenotypes in F1 hybrids. This was supported by the fact that the pharmacological overactivation of BDNF receptors altered the expression of its trans-regulated genes in the RA, thus disrupting the learned song structures of adult zebra finch songs at the acoustic and sequence levels. These results demonstrate functional neurogenetic associations between divergence in region-specific transcriptional regulation and species-specific learned behaviors.
Highlights
Species-specific behavior plays a role in a variety of inter- and intraspecific interactions, including reproduction and habitat use, in which species differences are thought to be an important factor in species co-occurrence [1,2,3]
By comparing the p-values of song feature differences between conspecific and cross-species song tutoring conditions, we found that song tutoring affected most of the song parameters, including syllable sequence and acoustics (Fig 2B and 2C)
We found that brain-derived neurotrophic factor (BDNF) was the most significant upstream trans-mediator of genes under trans-regulation in robust nucleus of the arcopallium (RA), which included genes for neural plasticity and dendritic spine formation (Fisher’s exact test, p = 6.44 × 10−7) (Fig 5B and 5C and S7 Fig)
Summary
Species-specific behavior plays a role in a variety of inter- and intraspecific interactions, including reproduction and habitat use, in which species differences are thought to be an important factor in species co-occurrence [1,2,3] Such species-specific behaviors can arise via species differences in the structure and development of the neural circuits underlying behavior [4,5,6]. The production of syllable acoustics and sequence is mainly regulated by the robust nucleus of the arcopallium (RA) and the song nuclei HVC (proper name), respectively, in the vocal motor circuit of the song system (Fig 1B) [22,23,24] The importance of these song nuclei in determining species-specific song traits suggests an underlying causative role of species differences in the structure and activity of these regions. A key gap in our knowledge is how species-specific patterns of gene expression in these regions arise via regulatory differences between species
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