Genomics analysis of potassium channel genes in songbirds reveals molecular specializations of brain circuits for the maintenance and production of learned vocalizations.
Genomics analysis of potassium channel genes in songbirds reveals molecular specializations of brain circuits for the maintenance and production of learned vocalizations.
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DOI：
10.1186/1471-2164-14-470
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发表时间：
2013-07-11
期刊：
影响因子：
4.4
通讯作者：
Mello CV
中科院分区：
文献类型：
--
作者：
Lovell PV;Carleton JB;Mello CV
分子神经生物学的一个基本问题是，决定基本神经元特性的基因如何塑造复杂学习行为背后的大脑回路的功能组织。鉴于完整脊椎动物基因组的可用性不断增加，比较基因组学代表了解决这一问题的一种有前途的方法。在这里，我们使用基因组学和分子方法来研究离子通道基因如何影响调节鸟鸣的大脑电路的特性，鸟鸣是一种习得的声音行为，与人类语音习得具有重要的相似性。我们重点关注钾 (K-) 通道，它是神经元细胞兴奋性的主要决定因素。从人类 K 通道基因组开始，我们使用跨物种 mRNA/蛋白质比对和同线分析来定义完整的直系同源物、旁系同源物、等位基因变体，以及斑胸草雀 (Taeniopygia guttata) 基因组中以前未预测到的新位点。我们还比较了鸡和斑胸草雀直向同源物中的蛋白质编码结构域，以识别正选择压力下的基因，以及那些在功能结构域中包含谱系特异性插入/缺失的基因。最后，我们进行了全面的原位杂交以确定大脑表达的程度，并鉴定了鸟类鸣叫系统细胞核中 K 通道基因的富集程度。我们鉴定了 107 个 K 通道雀基因，包括非哺乳动物脊椎动物谱系常见的 6 个新基因。鸣禽、鸟类或蜥脚类动物中不存在 20 种人类基因，或者是哺乳动物所独有的，这表明 K 通道特性可能具有谱系特异性。我们还确定了与非声音学习者鸡相比具有插入/缺失和/或高 dN/dS 比率的特定家庭成员。原位杂交显示，虽然大多数 K 通道基因在大脑中广泛表达，但有一个子集选择性地在歌曲核中表达，代表了发声电路的分子特化。总之，这些发现为调节鸣叫电路的生物物理和兴奋特性的基因提供了新的线索，确定了操纵鸣叫系统的潜在目标，并揭示了可能与鸟类发声学习和相关大脑区域的出现有关的基因组特化。
A fundamental question in molecular neurobiology is how genes that determine basic neuronal properties shape the functional organization of brain circuits underlying complex learned behaviors. Given the growing availability of complete vertebrate genomes, comparative genomics represents a promising approach to address this question. Here we used genomics and molecular approaches to study how ion channel genes influence the properties of the brain circuitry that regulates birdsong, a learned vocal behavior with important similarities to human speech acquisition. We focused on potassium (K-)Channels, which are major determinants of neuronal cell excitability. Starting with the human gene set of K-Channels, we used cross-species mRNA/protein alignments, and syntenic analysis to define the full complement of orthologs, paralogs, allelic variants, as well as novel loci not previously predicted in the genome of zebra finch (Taeniopygia guttata). We also compared protein coding domains in chicken and zebra finch orthologs to identify genes under positive selective pressure, and those that contained lineage-specific insertions/deletions in functional domains. Finally, we conducted comprehensive in situ hybridizations to determine the extent of brain expression, and identify K-Channel gene enrichments in nuclei of the avian song system. We identified 107 K-Channel finch genes, including 6 novel genes common to non-mammalian vertebrate lineages. Twenty human genes are absent in songbirds, birds, or sauropsids, or unique to mammals, suggesting K-Channel properties may be lineage-specific. We also identified specific family members with insertions/deletions and/or high dN/dS ratios compared to chicken, a non-vocal learner. In situ hybridization revealed that while most K-Channel genes are broadly expressed in the brain, a subset is selectively expressed in song nuclei, representing molecular specializations of the vocal circuitry. Together, these findings shed new light on genes that may regulate biophysical and excitable properties of the song circuitry, identify potential targets for the manipulation of the song system, and reveal genomic specializations that may relate to the emergence of vocal learning and associated brain areas in birds.
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影响因子：
2.5
作者：
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通讯作者：
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影响因子：
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