Zhang Cui, Oguz Cihan, Huse Sue, Xia Lu, Wu Jian, Peng Yu-Chih, Smith Margaret, Chen Jack, Long Carole A, Lack Justin, Su Xin-Zhuan
Malaria Functional Genomics Section, Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Disease, National Institutes of Health, Bethesda, MD, 20892-8132, USA.
NIAID Collaborative Bioinformatics Resource (NCBR), Frederick National Laboratory for Cancer Research, Leidos Biomedical Research, Inc., Frederick, MD, 21702, USA.
BMC Genomics. 2021 Apr 26;22(1):303. doi: 10.1186/s12864-021-07555-9.
Rodent malaria parasites are important models for studying host-malaria parasite interactions such as host immune response, mechanisms of parasite evasion of host killing, and vaccine development. One of the rodent malaria parasites is Plasmodium yoelii, and multiple P. yoelii strains or subspecies that cause different disease phenotypes have been widely employed in various studies. The genomes and transcriptomes of several P. yoelii strains have been analyzed and annotated, including the lethal strains of P. y. yoelii YM (or 17XL) and non-lethal strains of P. y. yoelii 17XNL/17X. Genomic DNA sequences and cDNA reads from another subspecies P. y. nigeriensis N67 have been reported for studies of genetic polymorphisms and parasite response to drugs, but its genome has not been assembled and annotated.
We performed genome sequencing of the N67 parasite using the PacBio long-read sequencing technology, de novo assembled its genome and transcriptome, and predicted 5383 genes with high overall annotation quality. Comparison of the annotated genome of the N67 parasite with those of YM and 17X parasites revealed a set of genes with N67-specific orthology, expansion of gene families, particularly the homologs of the Plasmodium chabaudi erythrocyte membrane antigen, large numbers of SNPs and indels, and proteins predicted to interact with host immune responses based on their functional domains.
The genomes of N67 and 17X parasites are highly diverse, having approximately one polymorphic site per 50 base pairs of DNA. The annotated N67 genome and transcriptome provide searchable databases for fast retrieval of genes and proteins, which will greatly facilitate our efforts in studying the parasite biology and gene function and in developing effective control measures against malaria.
啮齿动物疟原虫是研究宿主-疟原虫相互作用的重要模型，如宿主免疫反应、疟原虫逃避宿主杀伤的机制以及疫苗开发。约氏疟原虫是啮齿动物疟原虫之一，多种导致不同疾病表型的约氏疟原虫菌株或亚种已广泛应用于各种研究。已经对几种约氏疟原虫菌株的基因组和转录组进行了分析和注释，包括约氏疟原虫约氏亚种YM（或17XL）的致死菌株和约氏疟原虫17XNL/17X的非致死菌株。另一个亚种约氏疟原虫尼日尔亚种N67的基因组DNA序列和cDNA读数已被报道用于遗传多态性和寄生虫对药物反应的研究，但其基因组尚未组装和注释。
我们使用PacBio长读长测序技术对N67寄生虫进行了基因组测序，从头组装了其基因组和转录组，并预测了5383个基因，总体注释质量较高。将N67寄生虫的注释基因组与YM和17X寄生虫的注释基因组进行比较，发现了一组具有N67特异性直系同源性的基因、基因家族的扩展，特别是查巴迪疟原虫红细胞膜抗原的同源物、大量的单核苷酸多态性（SNP）和插入缺失，以及基于其功能域预测与宿主免疫反应相互作用的蛋白质。
N67和17X寄生虫的基因组高度多样，每50个碱基对的DNA中约有一个多态性位点。注释后的N67基因组和转录组提供了可搜索的数据库，用于快速检索基因和蛋白质，这将极大地促进我们研究寄生虫生物学和基因功能以及制定有效的疟疾控制措施的努力。
