Filarial nematodes, such as Brugia malayi, cause major health problems worldwide. The lack of a vaccine against B. malayi, combined with ineffective chemotherapy against the adult has prompted the examination of biogenic amine receptors (BARs) as possible targets for drug discovery. We employed bioinformatics to identify genes encoding putative B. malayi BARs. Surprisingly, the B. malayi genome contains half of the genes predicted to encode BARs in the genomes of free-living nematodes such as Caenorhabditis elegans or C. briggsae; however, all of the predicted B. malayi receptors have clear orthologues in C. elegans. The B. malayi genes encode each of the major BAR subclasses, including three serotonin, two dopamine and two tyramine/octopamine receptors and the structure of orthologous BAR genes is conserved. We find that potential G-protein coupling and ligand-specificity of individual BARs may be predicted by phylogenetic comparisons. Our results provide a framework for how G-protein coupled receptors may be targeted for drug development in medically important parasitic nematodes.

中文翻译：

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在寄生线虫 Brugia malayi 中编码假定的生物胺受体的基因。

丝虫线虫，如马来丝虫，在世界范围内引起严重的健康问题。缺乏针对马来亚双歧杆菌的疫苗，再加上对成人无效的化学疗法，促使人们将生物胺受体 (BAR) 作为药物发现的可能目标进行检查。我们采用生物信息学来识别编码假定的马来双歧杆菌 BAR 的基因。令人惊讶的是，马来亚双歧杆菌基因组包含一半的预测基因，这些基因在自由生活的线虫（例如秀丽隐杆线虫或 C. briggsae）的基因组中编码 BAR；然而，所有预测的马来亚双歧杆菌受体在秀丽隐杆线虫中都有明确的直系同源物。B. malayi 基因编码每个主要的 BAR 亚类，包括三种血清素、两种多巴胺和两种酪胺/章鱼胺受体，并且直向同源 BAR 基因的结构是保守的。我们发现个体 BAR 的潜在 G 蛋白偶联和配体特异性可以通过系统发育比较来预测。我们的研究结果为 G 蛋白偶联受体如何靶向医学上重要的寄生线虫的药物开发提供了一个框架。