Genomic organization and splicing evolution of the doublesex gene, a Drosophila regulator of sexual differentiation, in the dengue and yellow fever mosquito Aedes aegypti.
Genomic organization and splicing evolution of the doublesex gene, a Drosophila regulator of sexual differentiation, in the dengue and yellow fever mosquito Aedes aegypti.
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DOI：
10.1186/1471-2148-11-41
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发表时间：
2011-02-10
影响因子：
3.4
通讯作者：
Saccone G
中科院分区：
文献类型：
--
作者：
Salvemini M;Mauro U;Lombardo F;Milano A;Zazzaro V;Arcà B;Polito LC;Saccone G
在黑腹果蝇的模式系统中，双性基因(Dsx)是位于体细胞性别决定级联底部的双开关基因，它决定了性二型性状的分化。DSX的同源物在各种双翅目物种中功能保守，包括疟疾媒介冈比亚按蚊。它们显示出基于选择性剪接的性别特异性调控和编码的性别特异性蛋白的显著保守性，性别特异性蛋白是下游末端基因的转录调节因子，影响细胞、组织和器官的性别分化。在这项工作中，我们报告了登革热和黄热病媒介埃及伊蚊(Aeadsx)中DSX同源物的分子特征。Aeadsx通过选择性剪接产生性别特异的转录本，其编码的异构体与冈比亚按蚊和果蝇的同源物具有高度的同源性。有趣的是，Aeadsx产生了另一种新的女性特有的剪接变体。伊蚊和按蚊dsx基因的基因组比较分析表明，外显子组织的部分保守性和内含子长度的广泛差异。表达分析表明，Aeadsx转录本存在于发育的早期阶段，性别特异性调节至少从幼虫后期开始。对女性特异性非翻译区(UTR)的分析导致了可能参与性别特异性剪接调控的推测的顺式元件的鉴定。与其他双翅目物种相比，伊蚊DSX性别特异性剪接调控似乎更加复杂，这表明其调控以及上游剪接调控因子的招募的进化轨迹略有新奇。本研究揭示了埃及伊蚊与冈比亚按蚊同源基因的剪接调控的分子进化。在埃及伊蚊中，Dsx基因是性别特异的，编码两种雌性特异的和一种雄性特异的亚型，它们都共享一个含有双性/单抗-3(DM)结构域的N-末端和不同的C-末端。性别特异性调控是基于外显子跳跃、5‘端选择性剪接位点选择以及最有可能的选择性多聚腺苷化的组合。有趣的是，当将Aeadsx基因与按蚊dsx同源基因进行比较时，在电子预测的默认剪接事件和受调控的性别特异性剪接事件中存在差异，这表明上游调控因子要么不同，要么作用方式略有不同。此外，这项研究也为今后开发可用于不育昆虫技术(SIT)的转基因蚊子性别鉴定品系奠定了基础。
In the model system Drosophila melanogaster, doublesex (dsx) is the double-switch gene at the bottom of the somatic sex determination cascade that determines the differentiation of sexually dimorphic traits. Homologues of dsx are functionally conserved in various dipteran species, including the malaria vector Anopheles gambiae. They show a striking conservation of sex-specific regulation, based on alternative splicing, and of the encoded sex-specific proteins, which are transcriptional regulators of downstream terminal genes that influence sexual differentiation of cells, tissues and organs. In this work, we report on the molecular characterization of the dsx homologue in the dengue and yellow fever vector Aedes aegypti (Aeadsx). Aeadsx produces sex-specific transcripts by alternative splicing, which encode isoforms with a high degree of identity to Anopheles gambiae and Drosophila melanogaster homologues. Interestingly, Aeadsx produces an additional novel female-specific splicing variant. Genomic comparative analyses between the Aedes and Anopheles dsx genes revealed a partial conservation of the exon organization and extensive divergence in the intron lengths. An expression analysis showed that Aeadsx transcripts were present from early stages of development and that sex-specific regulation starts at least from late larval stages. The analysis of the female-specific untranslated region (UTR) led to the identification of putative regulatory cis-elements potentially involved in the sex-specific splicing regulation. The Aedes dsx sex-specific splicing regulation seems to be more complex with the respect of other dipteran species, suggesting slightly novel evolutionary trajectories for its regulation and hence for the recruitment of upstream splicing regulators. This study led to uncover the molecular evolution of Aedes aegypti dsx splicing regulation with the respect of the more closely related Culicidae Anopheles gambiae orthologue. In Aedes aegypti, the dsx gene is sex-specifically regulated and encodes two female-specific and one male-specific isoforms, all sharing a doublesex/mab-3 (DM) domain-containing N-terminus and different C-termini. The sex-specific regulation is based on a combination of exon skipping, 5' alternative splice site choice and, most likely, alternative polyadenylation. Interestingly, when the Aeadsx gene is compared to the Anopheles dsx ortholog, there are differences in the in silico predicted default and regulated sex-specific splicing events, which suggests that the upstream regulators either are different or act in a slightly different manner. Furthermore, this study is a premise for the future development of transgenic sexing strains in mosquitoes useful for sterile insect technique (SIT) programs.
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影响因子：
3.7
作者：
Fernanda Ruiz, Maria;Milano, Andreina;Salvemini, Marco;Maria Eirin-Lopez, Jose;Perondini, Andre L. P.;Selivon, Denise;Polito, Catello;Saccone, Giuseppe;Sanchez, Lucas
通讯作者：
Sanchez, Lucas
DOI：
10.1073/pnas.1000251107
发表时间：
2010-03-09
影响因子：
11.1
作者：
Fu, Guoliang;Lees, Rosemary S.;Alphey, Luke
通讯作者：
Alphey, Luke
影响因子：
64.5
作者：
BURTIS, KC;BAKER, BS
通讯作者：
BAKER, BS
影响因子：
10.7
作者：
Bertossa, Rinaldo C.;van de Zande, Louis;Beukeboom, Leo W.
通讯作者：
Beukeboom, Leo W.
影响因子：
4.8
作者：
Cho, S;Wensink, PC
通讯作者：
Wensink, PC