Institute of Evolutionary Biology (UPF-CSIC), PRBB, 08003 Barcelona, Spain.
BGI-Shenzhen, Shenzhen 518083, China.
Genome Res. 2022 Aug 25;32(8):1448-1462. doi: 10.1101/gr.276395.121.
Transcriptomic diversity greatly contributes to the fundamentals of disease, lineage-specific biology, and environmental adaptation. However, much of the actual isoform repertoire contributing to shaping primate evolution remains unknown. Here, we combined deep long- and short-read sequencing complemented with mass spectrometry proteomics in a panel of lymphoblastoid cell lines (LCLs) from human, three other great apes, and rhesus macaque, producing the largest full-length isoform catalog in primates to date. Around half of the captured isoforms are not annotated in their reference genomes, significantly expanding the gene models in primates. Furthermore, our comparative analyses unveil hundreds of transcriptomic innovations and isoform usage changes related to immune function and immunological disorders. The confluence of these evolutionary innovations with signals of positive selection and their limited impact in the proteome points to changes in alternative splicing in genes involved in immune response as an important target of recent regulatory divergence in primates.
转录组多样性极大地影响着疾病的基础、谱系特异性生物学和环境适应。然而，对于塑造灵长类动物进化有贡献的实际异构体组合仍有许多未知。在这里，我们在一组来自人类、三种其他大猿类和恒河猴的淋巴母细胞系（LCL）中结合了深度长读和短读测序，并辅以质谱蛋白质组学，产生了迄今为止灵长类动物中最大的全长异构体目录。大约一半的捕获异构体在其参考基因组中没有注释，这显著扩展了灵长类动物的基因模型。此外，我们的比较分析揭示了数百种与免疫功能和免疫性疾病相关的转录组创新和异构体使用变化。这些进化创新与正选择信号的融合，以及它们在蛋白质组中的有限影响，表明与免疫反应相关的基因中的可变剪接是灵长类动物最近调节分化的一个重要目标。
