Milani Liliana, Ghiselli Fabrizio, Maurizii Maria Gabriella, Nuzhdin Sergey V, Passamonti Marco
Dipartimento di Scienze Biologiche, Geologiche ed Ambientali, University of Bologna, Italy.
Genome Biol Evol. 2014 Feb;6(2):391-405. doi: 10.1093/gbe/evu021.
Mitochondrial ORFans (open reading frames having no detectable homology and with unknown function) were discovered in bivalve molluscs with doubly uniparental inheritance (DUI) of mitochondria. In these animals, two mitochondrial lineages are present, one transmitted through eggs (F-type), the other through sperm (M-type), each showing a specific ORFan. In this study, we used in situ hybridization and immunocytochemistry to provide evidence for the expression of Ruditapes philippinarum male-specific ORFan (orf21): both the transcript and the protein (RPHM21) were localized in spermatogenic cells and mature spermatozoa; the protein was localized in sperm mitochondria and nuclei, and in early embryos. Also, in silico analyses of orf21 flanking region and RPHM21 structure supported its derivation from viral sequence endogenization. We propose that RPHM21 prevents the recognition of M-type mitochondria by the degradation machinery, allowing their survival in the zygote. The process might involve a mechanism similar to that of Modulators of Immune Recognition, viral proteins involved in the immune recognition pathway, to which RPHM21 showed structural similarities. A viral origin of RPHM21 may also support a developmental role, because some integrated viral elements are involved in development and sperm differentiation of their host. Mitochondrial ORFans could be responsible for or participate in the DUI mechanism and their viral origin could explain the acquired capability of M-type mitochondria to avoid degradation and invade the germ line, that is what viruses do best: to elude host immune system and proliferate.
线粒体孤儿基因（开放阅读框，无可检测的同源性且功能未知）是在具有线粒体双亲单亲遗传（DUI）的双壳贝类中发现的。在这些动物中，存在两个线粒体谱系，一个通过卵子传递（F型），另一个通过精子传递（M型），每个谱系都显示出一个特定的孤儿基因。在本研究中，我们使用原位杂交和免疫细胞化学方法为菲律宾蛤仔雄性特异性孤儿基因（orf21）的表达提供证据：转录本和蛋白质（RPHM21）都定位于生精细胞和成熟精子中；该蛋白质定位于精子线粒体和细胞核以及早期胚胎中。此外，对orf21侧翼区域和RPHM21结构的电子分析支持其源自病毒序列内源性化。我们提出，RPHM21可防止降解机制识别M型线粒体，从而使其在合子中存活。该过程可能涉及一种类似于免疫识别调节因子的机制，免疫识别调节因子是参与免疫识别途径的病毒蛋白，RPHM21与之具有结构相似性。RPHM21的病毒起源也可能支持其发育作用，因为一些整合的病毒元件参与其宿主的发育和精子分化。线粒体孤儿基因可能负责或参与DUI机制，其病毒起源可以解释M型线粒体获得的避免降解和侵入生殖系的能力，而这正是病毒最擅长的：躲避宿主免疫系统并增殖。
