INRAE, LPGP UR1037, Fish Physiology and Genomics, Campus de Beaulieu, F-35000 Rennes, France.
Cells. 2022 Aug 30;11(17):2694. doi: 10.3390/cells11172694.
The gene plays major roles during brain development and is associated with various neuropathologies including autism. Data in non-mammalian species are scarce, and the aim of our study was to provide a comprehensive analysis of evolution in teleost fish, which are widely used for in vivo functional analysis and biomedical purposes. Comparative genomics in 78 species showed that and originate from the teleost-specific whole genome duplication (TGD). which is highly similar to human AUTS2, was almost systematically retained following TGD. In contrast, which encodes for a shorter protein similar to a short human AUTS2 isoform, was lost more frequently and independently during evolution. RNA-seq analysis in 10 species revealed a highly conserved profile with predominant expression of both genes in the embryo, brain, and gonads. Based on protein length, conserved domains, and expression profiles, we speculate that the long human isoform functions were retained by , while the short isoform functions were retained by and/or , depending on the lineage/species. showed a burst in expression during medaka brain formation, where it was expressed in areas of the brain associated with neurodevelopmental disorders. Together, our data suggest a strong conservation of functions in vertebrates despite different evolutionary scenarios in teleosts.
该基因在大脑发育过程中发挥主要作用，与包括自闭症在内的各种神经病理学有关。非哺乳动物物种的数据很少，我们的研究目的是对广泛用于体内功能分析和生物医学目的的硬骨鱼类进行全面的进化分析。对 78 个物种的比较基因组学研究表明， 和 起源于硬骨鱼特异性全基因组复制（TGD）。 与人类 AUTS2 高度相似，几乎在 TGD 后系统地保留下来。相比之下，编码与人 AUTS2 短亚型相似的较短蛋白质的 ，在进化过程中更频繁且独立丢失。在 10 个物种中的 RNA-seq 分析显示出高度保守的图谱，两个基因在胚胎、大脑和性腺中都有优势表达。基于蛋白质长度、保守结构域和表达谱，我们推测 保留了人类长亚型的功能，而短亚型的功能则由 和/或 保留，这取决于谱系/物种。 在日本青鳉脑形成过程中表达量激增，在与神经发育障碍相关的大脑区域表达。总之，我们的数据表明，尽管硬骨鱼的进化情况不同，但脊椎动物中 的功能仍具有很强的保守性。
