Hundreds of cell types form the vertebrate brain, but it is largely unknown how similar these cellular repertoires are between or within species, or how cell type diversity evolves. To examine cell type diversity across and within species, we performed single-cell RNA sequencing of ~130,000 hypothalamic cells from zebrafish (Danio rerio) and surface- and cave-morphs of Mexican tetra (Astyanax mexicanus). We found that over 75% of cell types were shared between zebrafish and Mexican tetra, which last shared a common ancestor over 150 million years ago. Orthologous cell types displayed differential paralogue expression that was generated by sub-functionalization after genome duplication. Expression of terminal effector genes, such as neuropeptides, was more conserved than the expression of their associated transcriptional regulators. Species-specific cell types were enriched for the expression of species-specific genes, and characterized by the neo-functionalization of members of recently expanded or contracted gene families. Within species comparisons revealed differences in immune repertoires and transcriptional changes in neuropeptidergic cell types associated with genomic differences between surface- and cave-morphs. The single-cell atlases presented here are a powerful resource to explore hypothalamic cell types, and reveal how gene family evolution and the neo- and sub-functionalization of paralogs contribute to cellular diversity.

中文翻译：

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基因家族进化是硬骨鱼下丘脑细胞类型多样化的基础

成百上千的细胞类型形成了脊椎动物的大脑，但是在很大程度上这些物种之间或内部的细胞组成如何相似，或者细胞类型的多样性如何进化，尚不清楚。为了检查物种之间和物种内部的细胞类型多样性，我们对斑马鱼（Danio rerio）以及墨西哥四（Astyanax mexicanus）的表面和洞穴形态的约130,000个下丘脑细胞进行了单细胞RNA测序。我们发现，斑马鱼和墨西哥四胞胎之间共享超过75％的细胞类型，而后者在1.5亿年前共享一个共同祖先。直系同源细胞类型显示差异旁系同源表达，这是基因组复制后亚功能化产生的。末端效应基因如神经肽的表达比其相关转录调节子的表达更保守。物种特异性细胞类型丰富了物种特异性基因的表达，并以最近扩展或收缩的基因家族成员的新功能为特征。在物种内进行的比较揭示了免疫组成的差异以及神经肽能细胞类型的转录变化，这些变化与表面和洞穴形态之间的基因组差异有关。本文介绍的单细胞图谱是探索下丘脑细胞类型的强大资源，并揭示了基因家族的进化以及旁系同源物的新功能和亚功能化如何促进细胞多样性。在物种内进行的比较揭示了免疫组成的差异以及神经肽能细胞类型的转录变化，这些变化与表面和洞穴形态之间的基因组差异有关。本文介绍的单细胞图谱是探索下丘脑细胞类型的强大资源，并揭示了基因家族的进化以及旁系同源物的新功能和亚功能化如何促进细胞多样性。在物种内进行的比较揭示了免疫组成的差异以及神经肽能细胞类型的转录变化，这些变化与表面和洞穴形态之间的基因组差异有关。本文介绍的单细胞图谱是探索下丘脑细胞类型的强大资源，并揭示了基因家族的进化以及旁系同源物的新功能和亚功能化如何促进细胞多样性。