近日，德国马克斯·普朗克分子遗传学研究所Darío G. Lupiáñez、Stefan Mundlos等研究人员合作通过鼹鼠基因组发现，调控重排与适应性雌雄间性相关。 2020年10月9日，国际知名学术期刊《科学》发表了这一成果。

研究人员使用系统生物学的策略来研究了哺乳动物的独特特征：雌性鼹鼠中男性化卵睾体的发育。通过结合伊比利亚鼹鼠（Talpa occidentalis）染色体规模的基因组组装，与转录组、表观遗传学和染色质相互作用数据集，研究人员发现重排改变具有不同性腺表达模式的基因监管图谱。

其中包括涉及CYP17A1的串联重复，控制雄激素合成的基因以及涉及睾丸前生长因子基因FGF9的染色体内倒置，该基因在葡萄胎卵母细胞中表达。具有敲入鼹鼠CYP17A1增强子或过表达FGF9的转基因小鼠表现出表型重现鼹鼠的性特征。

这些结果突出了整合基因组方法如何揭示非编码序列变化的表型影响。

据介绍，将基因组变异与表型性状联系起来仍然是进化遗传学的主要挑战。

附：英文原文

Title: The mole genome reveals regulatory rearrangements associated with adaptive intersexuality

Author: Francisca M. Real, Stefan A. Haas, Paolo Franchini, Peiwen Xiong, Oleg Simakov, Heiner Kuhl, Robert Schpflin, David Heller, M-Hossein Moeinzadeh, Verena Heinrich, Thomas Krannich, Annkatrin Bressin, Michaela F. Hartmann, Stefan A. Wudy, Dina K. N. Dechmann, Alicia Hurtado, Francisco J. Barrionuevo, Magdalena Schindler, Izabela Harabula, Marco Osterwalder, Michael Hiller, Lars Wittler, Axel Visel, Bernd Timmermann, Axel Meyer, Martin Vingron, Rafael Jiménez, Stefan Mundlos, Darío G. Lupiáez

Issue&Volume: 2020/10/09

Abstract: Linking genomic variation to phenotypical traits remains a major challenge in evolutionary genetics. In this study, we use phylogenomic strategies to investigate a distinctive trait among mammals: the development of masculinizing ovotestes in female moles. By combining a chromosome-scale genome assembly of the Iberian mole, Talpa occidentalis, with transcriptomic, epigenetic, and chromatin interaction datasets, we identify rearrangements altering the regulatory landscape of genes with distinct gonadal expression patterns. These include a tandem triplication involving CYP17A1, a gene controlling androgen synthesis, and an intrachromosomal inversion involving the pro-testicular growth factor gene FGF9, which is heterochronically expressed in mole ovotestes. Transgenic mice with a knock-in mole CYP17A1 enhancer or overexpressing FGF9 showed phenotypes recapitulating mole sexual features. Our results highlight how integrative genomic approaches can reveal the phenotypic impact of noncoding sequence changes.

DOI: 10.1126/science.aaz2582

Source: https://science.sciencemag.org/content/370/6513/208