Institute for Cell and Molecular Biosciences, The Medical School, Newcastle University, Newcastle upon Tyne, United Kingdom.
PLoS Pathog. 2012;8(10):e1002979. doi: 10.1371/journal.ppat.1002979. Epub 2012 Oct 25.
The dynamics of reductive genome evolution for eukaryotes living inside other eukaryotic cells are poorly understood compared to well-studied model systems involving obligate intracellular bacteria. Here we present 8.5 Mb of sequence from the genome of the microsporidian Trachipleistophora hominis, isolated from an HIV/AIDS patient, which is an outgroup to the smaller compacted-genome species that primarily inform ideas of evolutionary mode for these enormously successful obligate intracellular parasites. Our data provide detailed information on the gene content, genome architecture and intergenic regions of a larger microsporidian genome, while comparative analyses allowed us to infer genomic features and metabolism of the common ancestor of the species investigated. Gene length reduction and massive loss of metabolic capacity in the common ancestor was accompanied by the evolution of novel microsporidian-specific protein families, whose conservation among microsporidians, against a background of reductive evolution, suggests they may have important functions in their parasitic lifestyle. The ancestor had already lost many metabolic pathways but retained glycolysis and the pentose phosphate pathway to provide cytosolic ATP and reduced coenzymes, and it had a minimal mitochondrion (mitosome) making Fe-S clusters but not ATP. It possessed bacterial-like nucleotide transport proteins as a key innovation for stealing host-generated ATP, the machinery for RNAi, key elements of the early secretory pathway, canonical eukaryotic as well as microsporidian-specific regulatory elements, a diversity of repetitive and transposable elements, and relatively low average gene density. Microsporidian genome evolution thus appears to have proceeded in at least two major steps: an ancestral remodelling of the proteome upon transition to intracellular parasitism that involved reduction but also selective expansion, followed by a secondary compaction of genome architecture in some, but not all, lineages.
与研究充分的涉及专性细胞内细菌的模式系统相比，生活在其他真核细胞内的真核生物的还原基因组进化动态还了解甚少。在这里，我们展示了来自 HIV/AIDS 患者的微孢子虫 Trachipleistophora hominis 基因组的 8.5Mb 序列，它是较小的紧凑型基因组物种的外群，这些物种主要为这些极其成功的专性细胞内寄生虫的进化模式提供了信息。我们的数据提供了更大的微孢子虫基因组的基因组成、基因组结构和基因间区的详细信息，而比较分析使我们能够推断出所研究物种的共同祖先的基因组特征和代谢。在共同祖先中，基因长度的减少和代谢能力的大量丧失伴随着新的微孢子虫特异性蛋白家族的进化，这些蛋白家族在微孢子虫中的保守性，在还原进化的背景下，表明它们可能在其寄生生活方式中具有重要功能。祖先已经失去了许多代谢途径，但保留了糖酵解和戊糖磷酸途径，以提供细胞质 ATP 和还原辅酶，并且它有一个最小的线粒体（mitosome），产生 Fe-S 簇但不产生 ATP。它具有类似于细菌的核苷酸转运蛋白，作为窃取宿主产生的 ATP 的关键创新，RNAi 的机制，早期分泌途径的关键要素，经典的真核生物以及微孢子虫特异性调节元件，多样化的重复和转座元件，以及相对较低的平均基因密度。因此，微孢子虫的基因组进化似乎至少经历了两个主要步骤：在过渡到细胞内寄生时，蛋白质组发生了祖先重塑，这涉及到减少但也有选择性的扩张，随后在一些但不是所有谱系中，基因组结构发生了二次压缩。
