femaleless Controls Sex Determination and Dosage Compensation Pathways in Females of Anopheles Mosquitoes.
femaleless Controls Sex Determination and Dosage Compensation Pathways in Females of Anopheles Mosquitoes.
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DOI：
10.1016/j.cub.2020.12.014
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发表时间：
2021-03-08
期刊：
影响因子：
--
通讯作者：
Krzywinski J
中科院分区：
文献类型：
--
作者：
Krzywinska E;Ferretti L;Li J;Li JC;Chen CH;Krzywinski J
昆虫的性别决定和密切相关的剂量补偿途径代表了一个具有挑战性的进化难题，已经解决了只有在果蝇。在非果蝇分类群中鉴定的果蝇基因的直系同源物的分析表明，性别决定途径的进化与自下而上的模式是一致的，其中只有通路内的末端基因是很好地保守的。doublemex（dsx）是一个古老的性别决定基因，存在于所有研究的物种中，位于最底层，编码性别特异性蛋白，协调下游的性别分化过程。除鳞翅目昆虫外，已知其雌性特异性剪接受Transformer（tra）及其辅因子Transformer-2（tra 2）调节。在这里，我们表明，在非洲疟疾蚊子冈比亚按蚊，一个基因，这可能出现在按蚊谱系，我们称之为无雌性（fle），控制女性的性别决定通过调节dsx和fruitless（fru;另一个终端基因内的性别决定途径的分支）剪接。此外，fle代表了性别决定和剂量补偿途径之间的一种新的分子联系。这是必要的，以抑制激活的剂量补偿在女性中，表现为显着上调的女性X染色体基因和相关的女性特异性致死率，但没有负面影响男性，在响应fle敲低。这种意想不到的特性，结合按蚊中高度保守的序列和功能，使fle成为人类疟疾所有主要媒介遗传控制的极好靶标。fle是一种新的在按蚊中保守的性别决定途径元件fle可能起源于按蚊谱系并且在按蚊中高度保守fle抑制雌性中剂量补偿的激活fle转录物的消耗对雌性是致命的或有害的Krzywinska et al.确定了按蚊性别决定途径的一个新元素。除了控制dsx和fru的剪接之外，无雌性（fle）对于抑制雌性的剂量补偿和生存力是必需的。fle基因敲除后对雌性的有害作用使fle成为控制疟蚊的一个有希望的靶标。
The insect sex determination and the intimately linked dosage compensation pathways represent a challenging evolutionary puzzle that has been solved only in Drosophila melanogaster. Analyses of orthologs of the Drosophila genes identified in non-drosophilid taxa revealed that evolution of sex determination pathways is consistent with a bottom-up mode, where only the terminal genes within the pathway are well conserved. doublesex (dsx), occupying a bottom-most position and encoding sex-specific proteins orchestrating downstream sexual differentiation processes, is an ancient sex-determining gene present in all studied species. With the exception of lepidopterans, its female-specific splicing is known to be regulated by transformer (tra) and its co-factor transformer-2 (tra2). Here we show that in the African malaria mosquito Anopheles gambiae, a gene, which likely arose in the Anopheles lineage and which we call femaleless (fle), controls sex determination in females by regulating splicing of dsx and fruitless (fru; another terminal gene within a branch of the sex determination pathway). Moreover, fle represents a novel molecular link between the sex determination and dosage compensation pathways. It is necessary to suppress activation of dosage compensation in females, as demonstrated by the significant upregulation of the female X chromosome genes and a correlated female-specific lethality, but no negative effect on males, in response to fle knockdown. This unexpected property, combined with a high level of conservation in sequence and function in anopheline mosquitoes, makes fle an excellent target for genetic control of all major vectors of human malaria. fle is a new sex determination pathway element conserved in Anopheles mosquitoes fle may have originated in the Anopheles lineage and is highly conserved in Anopheles fle suppresses activation of dosage compensation in females Depletion of fle transcripts is lethal or otherwise deleterious to females Krzywinska et al. identify a new element of the sex determination pathway in Anopheles. femaleless (fle), in addition to controlling splicing of dsx and fru, is essential for suppression of dosage compensation and viability of females. Female-deleterious effects upon fle knockdown make fle a promising target for control of malaria mosquitoes.
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