A male-specific doublesex isoform reveals an evolutionary pathway of sexual development via distinct alternative splicing mechanisms.

A male-specific doublesex isoform reveals an evolutionary pathway of sexual development via distinct alternative splicing mechanisms.
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DOI:
10.1038/s42003-022-03664-7
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发表时间:
2022-07-22
影响因子:
5.9
通讯作者:
--
中科院分区:
生物学2区
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--
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doublemex/mab-3相关转录因子(Dmrt)基因调节后生动物的性发育。对昆虫,特别是黑腹果蝇中的dsx基因的研究表明,dsx的选择性剪接产生性别特异性的Dsx亚型,这是性别分化的基础。这种基于剪接的机制是性别特异性Dmrt功能的基础,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,但这种转变在进化过程中如何发生尚不清楚。在这里,我们确定了一个男性特异性dsx转录(dsxM 2)通过内含子保留(IR),除了以前确定的dsxM和dsxF转录通过交替多聚腺苷酸化(阿帕)与相互排斥的外显子。我们发现DsxM 2具有与DsxM相似的雄性化功能。我们还发现,IR为基础的机制,产生性别特异性dsx成绩单是保守的苍蝇蟑螂。进一步分析这些dsx成绩单提出了一个进化途径,从性单态性性别特异性dsx通过顺序使用IR为基础的和APA为基础的选择性剪接。通过内含子保留鉴定了一种祖先的雄性特异性doublex同种型dsxM 2,其雄性化功能弱于现代dsxM
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 (dsxM2) through intron retention (IR), in addition to previously identified dsxM and dsxF transcripts through alternative polyadenylation (APA) with mutually exclusive exons. We found that DsxM2 had similarly masculinizing function as DsxM. 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. An ancestral male-specific doublesex isoform, dsxM2, is identified via intron retention, with a masculinizing function weaker than the modern dsxM
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