Control of yeast retrotransposons mediated through nucleoporin evolution

Yeasts serve as hosts to several types of genetic parasites. Few studies have addressed the evolutionary trajectory of yeast genes that control the stable co-existence of these parasites with their host cell. In Saccharomyces yeasts, the retrovirus-like Ty retrotransposons must access the nucleus. We show that several genes encoding components of the yeast nuclear pore complex have experienced natural selection for substitutions that change the encoded protein sequence. By replacing these S. cerevisiae genes with orthologs from other Saccharomyces species, we discovered that natural sequence changes have affected the mobility of Ty retrotransposons. Specifically, changing the genetic sequence of NUP84 or NUP82 to match that of other Saccharomyces species alters the mobility of S. cerevisiae Ty1 and Ty3. Importantly, all tested housekeeping functions of NUP84 and NUP82 remained equivalent across species. Signatures of natural selection, resulting in altered interactions with viruses and parasitic genetic elements, are common in host defense proteins. Yet, few instances have been documented in essential housekeeping proteins. The nuclear pore complex is the gatekeeper of the nucleus. This study shows how the evolution of this large, ubiquitous eukaryotic complex can alter the replication of a molecular parasite, but concurrently maintain essential host functionalities regarding nucleocytoplasmic trafficking.酵母是多种遗传寄生虫的天然宿主。目前鲜有研究聚焦于调控这类寄生虫与宿主细胞稳定共存的酵母基因的进化轨迹。在酿酒酵母属（Saccharomyces）酵母中，逆转录病毒样Ty反转录转座子必须进入细胞核。本研究发现，编码酵母核孔复合物（nuclear pore complex, NPC）组分的多个基因，经历了自然选择作用，其编码的蛋白序列发生了氨基酸替换。我们将酿酒酵母（Saccharomyces cerevisiae）的这些基因替换为其他酿酒酵母属物种的直系同源基因后发现，自然发生的序列改变会影响Ty反转录转座子的迁移活性。具体而言，将NUP84或NUP82的基因序列修改为与其他酿酒酵母属物种一致时，会改变酿酒酵母Ty1与Ty3的迁移活性。值得注意的是，经检测的NUP84与NUP82的所有持家功能在不同物种间均保持一致。这类因自然选择产生、可改变宿主与病毒及遗传寄生虫互作模式的分子特征，在宿主防御蛋白中较为常见，但在必需持家蛋白中却鲜有报道。核孔复合物是细胞核的守门人。本研究揭示了这一庞大且广泛分布于真核生物中的复合物的进化历程，如何既能改变分子寄生虫的复制过程，又能同时维持宿主在核质穿梭方面的核心生理功能。