Department of Biochemistry, University at Buffalo-State University of New York, Buffalo, New York, USA.
Department of Biomedical Informatics, University at Buffalo-State University of New York, Buffalo, New York, USA.
Insect Mol Biol. 2021 Aug;30(4):410-419. doi: 10.1111/imb.12705. Epub 2021 Apr 27.
The success of transgenic mosquito vector control approaches relies on well-targeted gene expression, requiring the identification and characterization of a diverse set of mosquito promoters and transcriptional enhancers. However, few enhancers have been characterized in Anopheles gambiae to date. Here, we employ the SCRMshaw method we previously developed to predict enhancers in the A. gambiae genome, preferentially targeting vector-relevant tissues such as the salivary glands, midgut and nervous system. We demonstrate a high overall success rate, with at least 8 of 11 (73%) tested sequences validating as enhancers in an in vivo xenotransgenic assay. Four tested sequences drive expression in either the salivary gland or the midgut, making them directly useful for probing the biology of these infection-relevant tissues. The success of our study suggests that computational enhancer prediction should serve as an effective means for identifying A. gambiae enhancers with activity in tissues involved in malaria propagation and transmission.
转基因蚊子媒介控制方法的成功依赖于靶向良好的基因表达，这需要鉴定和表征一系列不同的蚊子启动子和转录增强子。然而，迄今为止，在冈比亚按蚊中仅对少数增强子进行了表征。在这里，我们采用我们之前开发的 SCRMshaw 方法来预测冈比亚按蚊基因组中的增强子，这些增强子优先靶向与载体相关的组织，如唾液腺、中肠和神经系统。我们证明了一种高的总体成功率，至少有 11 个测试序列中的 8 个（73%）在体内异种转基因试验中被验证为增强子。四个测试序列在唾液腺或中肠中驱动表达，这使它们直接可用于探测这些与感染相关的组织的生物学。我们的研究成功表明，计算增强子预测应该是一种有效的方法，可用于鉴定在疟疾传播和传播中涉及的组织中具有活性的冈比亚按蚊增强子。
