Ustyantsev K V, Vavilova V Yu, Blinov A G, Berezikov E V
Institute of Cytology and Genetics of Siberian Branch of the Russian Academy of Sciences, Novosibirsk, Russia.
Vavilovskii Zhurnal Genet Selektsii. 2021 Feb;25(1):108-116. doi: 10.18699/VJ21.013.
Hundreds of millions of people worldwide are infected by various species of parasitic flatworms. Without treatment, acute and chronical infections frequently lead to the development of severe pathologies and even death. Emerging data on a decreasing efficiency of some important anthelmintic compounds and the emergence of resistance to them force the search for alternative drugs. Parasitic flatworms have complex life cycles, are laborious and expensive in culturing, and have a range of anatomic and physiological adaptations that complicate the application of standard molecular-biological methods. On the other hand, free-living flatworm species, evolutionarily close to parasitic flatworms, do not have the abovementioned difficulties, which makes them potential alternative models to search for and study homologous genes. In this review, we describe the use of the basal free-living flatworm Macrostomum lignano as such a model. M. lignano has a number of convenient biological and experimental properties, such as fast reproduction, easy and non-expensive laboratory culturing, optical body transparency, obligatory sexual reproduction, annotated genome and transcriptome assemblies, and the availability of modern molecular methods, including transgenesis, gene knockdown by RNA interference, and in situ hybridization. All this makes M. lignano amenable to the most modern approaches of forward and reverse genetics, such as transposon insertional mutagenesis and methods of targeted genome editing by the CRISPR/Cas9 system. Due to the availability of an increasing number of genome and transcriptome assemblies of different parasitic flatworm species, new knowledge generated by studying M. lignano can be easily translated to parasitic flatworms with the help of modern bioinformatic methods of comparative genomics and transcriptomics. In support of this, we provide the results of our bioinformatics search and analysis of genes homologous between M. lignano and parasitic flatworms, which predicts a list of promising gene targets for subsequent research.
全球数亿人感染了各种寄生扁虫。未经治疗的急性和慢性感染常常导致严重病变的发展，甚至死亡。一些重要驱虫化合物的疗效下降以及对这些化合物产生抗性的新数据，促使人们寻找替代药物。寄生扁虫具有复杂的生命周期，培养起来费力且昂贵，并且具有一系列解剖学和生理学适应性，这使得标准分子生物学方法的应用变得复杂。另一方面，与寄生扁虫在进化上相近的自由生活扁虫物种没有上述困难，这使其成为寻找和研究同源基因的潜在替代模型。在本综述中，我们描述了使用基础自由生活扁虫秀丽隐杆线虫作为这样一个模型。秀丽隐杆线虫具有许多便利的生物学和实验特性，如繁殖快、实验室培养容易且成本低、身体光学透明、 obligatory 有性繁殖、有注释的基因组和转录组组装，以及包括转基因、通过RNA干扰进行基因敲除和原位杂交在内的现代分子方法的可用性。所有这些使得秀丽隐杆线虫适合采用最现代的正向和反向遗传学方法，如转座子插入诱变和通过CRISPR/Cas9系统进行靶向基因组编辑的方法。由于不同寄生扁虫物种的基因组和转录组组装数量不断增加，通过研究秀丽隐杆线虫产生的新知识可以借助比较基因组学和转录组学的现代生物信息学方法轻松转化到寄生扁虫身上。为此，我们提供了对秀丽隐杆线虫和寄生扁虫之间同源基因的生物信息学搜索和分析结果，该结果预测了一系列后续研究有前景的基因靶点。
