Thiruppathy Mathi, Teubner Lauren, Roberts Ryan R, Lasser Micaela C, Moscatello Alessandra, Chen Ya-Wen, Hochstim Christian, Ruffins Seth, Sarkar Arijita, Tassey Jade, Evseenko Denis, Lozito Thomas P, Willsey Helen Rankin, Gillis J Andrew, Crump J Gage
Department of Stem Cell Biology and Regenerative Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
Department of Psychiatry and Behavioral Sciences, Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA, USA.
Nature. 2025 Mar;639(8055):682-690. doi: 10.1038/s41586-024-08577-5. Epub 2025 Jan 9.
How new structures emerge during evolution has long fascinated biologists. An example is how the diminutive bones of the mammalian middle ear arose from ancestral fish jawbones. By contrast, the evolutionary origin of the outer ear, another mammalian innovation, remains a mystery, partly because it is supported by non-mineralized elastic cartilage, which is rarely recovered in fossils. Whether the outer ear arose de novo or through the reuse of ancestral developmental programs has remained unknown. Here we show that the outer ear shares gene regulatory programs with the gills of fishes and amphibians for both its initial outgrowth and the later development of the elastic cartilage. Comparative single-nucleus multiomics of the human outer ear and zebrafish gills reveals conserved gene expression and putative enhancers enriched for common transcription factor binding motifs. This is reflected by the transgenic activity of human outer-ear enhancers in gills, and of fish gill enhancers in the outer ear. Furthermore, single-cell multiomics of the cartilaginous book gills of horseshoe crabs reveals a developmental program shared with the distal-less homeobox (DLX)-mediated gill program of vertebrates, with a book-gill distal-less enhancer driving expression in zebrafish gills. We propose that elements of an invertebrate gill program were reutilized in vertebrates to generate first gills and then the outer ear.
在进化过程中，新结构是如何出现的，长期以来一直吸引着生物学家。一个例子是哺乳动物中耳的微小骨骼是如何从鱼类的祖先颌骨进化而来的。相比之下，外耳作为哺乳动物的另一项创新，其进化起源仍然是个谜，部分原因是它由非矿化的弹性软骨支撑，而这种软骨在化石中很少被保存下来。外耳是从头起源还是通过重新利用祖先的发育程序产生的，一直不为人知。在这里，我们表明，外耳在其最初的生长以及弹性软骨的后期发育过程中，与鱼类和两栖动物的鳃共享基因调控程序。对人类外耳和斑马鱼鳃进行比较单核多组学分析，揭示了保守的基因表达以及富含共同转录因子结合基序的推定增强子。这通过人类外耳增强子在鳃中的转基因活性以及鱼类鳃增强子在外耳中的转基因活性得到体现。此外，对鲎的软骨书鳃进行单细胞多组学分析，揭示了一个与脊椎动物由远端缺失同源框（DLX）介导的鳃程序共享的发育程序，其中一个书鳃远端缺失增强子在斑马鱼鳃中驱动基因表达。我们提出，脊椎动物重新利用了无脊椎动物鳃程序的元件，首先产生了鳃，然后产生了外耳。
