Claire Sayers, Vikash Pandey, Arjun Balakrishnan, Katharine Michie, Dennis Svedberg, Mirjam Hunziker, Mercedes Pardo, Jyoti Choudhary, Ronnie Berntsson, Oliver Billker
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引用次数: 0
摘要
疟原虫的有性生殖对其向蚊子的传播至关重要,并为了解性的进化提供了一个不同的真核生物模型。通过对伯格氏疟原虫进行基因筛选,我们发现了 348 个与性和传播相关的基因,并确定了未研究基因的作用,将其作为阻断传播的干预措施的潜在靶标。这些功能数据加深了我们对雌性代谢重编程、减数分裂和轴丝的理解。我们发现了一个由一个SUN结构域蛋白(SUN1)和一个推定的尿囊素酶(ALLC1)组成的复合物,该复合物在雄性配子发生过程中将微管组织中心与核包膜连接起来并促成有丝分裂纺锤体的形成,从而对雄性生育能力至关重要。这两种蛋白在小鼠睾丸中都有直向同源物,这些数据提出了非典型 SUN 结构域蛋白在连接细胞核和轴丝中扮演古老角色的可能性。总之,我们的数据为疟原虫传播的分子过程提供了一幅无偏见的图景。补充信息中包含了本文透明的同行评审过程记录。
Systematic screens for fertility genes essential for malaria parasite transmission reveal conserved aspects of sex in a divergent eukaryote.
Sexual reproduction in malaria parasites is essential for their transmission to mosquitoes and offers a divergent eukaryote model to understand the evolution of sex. Through a panel of genetic screens in Plasmodium berghei, we identify 348 sex and transmission-related genes and define roles for unstudied genes as putative targets for transmission-blocking interventions. The functional data provide a deeper understanding of female metabolic reprogramming, meiosis, and the axoneme. We identify a complex of a SUN domain protein (SUN1) and a putative allantoicase (ALLC1) that is essential for male fertility by linking the microtubule organizing center to the nuclear envelope and enabling mitotic spindle formation during male gametogenesis. Both proteins have orthologs in mouse testis, and the data raise the possibility of an ancient role for atypical SUN domain proteins in coupling the nucleus and axoneme. Altogether, our data provide an unbiased picture of the molecular processes that underpin malaria parasite transmission. A record of this paper's transparent peer review process is included in the supplemental information.