The Orthologue of the Fruitfly Sex Behaviour Gene <em>Fruitless</em> in the Mosquito <em>Aedes aegypti</em>: Evolution of Genomic Organisation and Alternative Splicing

In Drosophila melanogaster the doublesex (dsx) and fruitless (fru) regulatory genes act at the bottom of the somatic sex determination pathway. Both are regulated via alternative splicing by an upstream female-specific TRA/TRA-2 complex, recognizing a common cis element. dsx controls somatic sexual differentiation of non-neural as well as of neural tissues. fru, on the other hand, expresses male-specific functions only in neural system where it is required to built the neural circuits underlying proper courtship behaviour. In the mosquito Aedes aegypti sex determination is different from Drosophila. The key male determiner M, which is located on one of a pair of homomorphic sex chromosomes, controls sex-specific splicing of the mosquito dsx orthologue. In this study we report the genomic organization and expression of the fru homologue in Ae. aegypti (Aeafru). We found that it is sex-specifically spliced suggesting that it is also under the control of the sex determination pathway. Comparative analyses between the Aeafru and Anopheles gambiae fru (Angfru) genomic loci revealed partial conservation of exon organization and extensive divergence of intron lengths. We find that Aeadsx and Aeafru share novel cis splicing regulatory elements conserved in the alternatively spliced regions. We propose that in Aedes aegypti sex-specific splicing of dsx and fru is most likely under the control of splicing regulatory factors which are different from TRA and TRA-2 found in other dipteran insects and discuss the potential use of fru and dsx for developing new genetic strategies in vector control.在黑腹果蝇（Drosophila melanogaster）中，双性基因（doublesex，dsx）与无果基因（fruitless，fru）这两个调控基因位于体细胞性别决定通路的下游。二者均由上游的雌性特异型TRA/TRA-2复合物通过可变剪接进行调控，该复合物可识别共同的顺式作用元件。dsx可调控非神经组织与神经组织的体细胞性别分化。而fru仅在神经系统中发挥雄性特异功能，其对于构建正常求偶行为背后的神经环路是必需的。在埃及伊蚊（Aedes aegypti）中，性别决定机制与果蝇存在差异。位于一对同形性染色体之一上的关键雄性决定因子M，可调控埃及伊蚊dsx同源基因的性别特异性剪接。本研究报道了埃及伊蚊fru同源基因（Aeafru）的基因组结构与表达模式。我们发现该基因存在性别特异性剪接，提示其同样处于性别决定通路的调控之下。对Aeafru与冈比亚按蚊（Anopheles gambiae）fru基因（Angfru）的基因组位点进行比较分析后发现，二者的外显子结构存在部分保守性，而内含子长度则存在显著差异。我们发现，埃及伊蚊dsx基因（Aeadsx）与Aeafru共享一类新的、存在于可变剪接区域的保守剪接顺式调控元件。我们提出，埃及伊蚊中dsx与fru的性别特异性剪接，大概率受到与其他双翅目昆虫中TRA/TRA-2不同的剪接调控因子的控制，并讨论了利用fru与dsx开发媒介昆虫防治新型遗传策略的潜在可能。