The Key Laboratory of Developmental Genes and Human Disease, School of Life Science and Technology, Southeast University, Nanjing, 210096, China.
Co-innovation Center of Neuroregeneration, Nantong University, Nantong, 226019, China.
Commun Biol. 2022 Jul 22;5(1):728. doi: 10.1038/s42003-022-03664-7.
The doublesex/mab-3 related transcription factor (Dmrt) genes regulate sexual development in metazoans. Studies of the doublesex (dsx) gene in insects, in particular Drosophila melanogaster, reveal that alternative splicing of dsx generates sex-specific Dsx isoforms underlying sexual differentiation. Such a splicing-based mechanism underlying sex-specific Dmrt function is thought to be evolved from a transcription-based mechanism used in non-insect species, but how such transition occurs during evolution is not known. Here we identified a male-specific dsx transcript (dsx) through intron retention (IR), in addition to previously identified dsx and dsx transcripts through alternative polyadenylation (APA) with mutually exclusive exons. We found that Dsx had similarly masculinizing function as Dsx. We also found that the IR-based mechanism generating sex-specific dsx transcripts was conserved from flies to cockroaches. Further analysis of these dsx transcripts suggested an evolutionary pathway from sexually monomorphic to sex-specific dsx via the sequential use of IR-based and APA-based alternative splicing.
双性(mab-3 相关转录因子（Dmrt）基因调控后生动物的性发育。对昆虫，特别是黑腹果蝇中的 doublesex（dsx）基因的研究表明，dsx 的选择性剪接产生了性别特异性的 Dsx 同工型，为性分化提供了基础。这种基于剪接的性别特异性 Dmrt 功能的机制被认为是从非昆虫物种中使用的基于转录的机制进化而来的，但这种转变是如何在进化过程中发生的尚不清楚。在这里，我们通过内含子保留（IR）鉴定了一种雄性特异性 dsx 转录本（dsx），除了以前通过具有互斥外显子的选择性多聚腺苷酸化（APA）鉴定的 dsx 和 dsx 转录本。我们发现 Dsx 具有与 Dsx 相似的雄性化功能。我们还发现，从果蝇到蟑螂，产生性别特异性 dsx 转录本的基于 IR 的机制是保守的。对这些 dsx 转录本的进一步分析表明，通过基于 IR 的和基于 APA 的选择性剪接的顺序使用，从性单态到性别特异性 dsx 的进化途径。
