Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland, USA.
Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland, USA
J Virol. 2018 Aug 29;92(18). doi: 10.1128/JVI.00850-18. Print 2018 Sep 15.
The laboratory mouse gene encodes a retroviral restriction factor that mediates resistance to murine leukemia viruses (MLVs). Sequence similarity between and the protein of the murine endogenous retrovirus L (MuERV-L) family of ERVs suggests that was coopted from an ancient provirus. Previous evolutionary studies found orthologs only in the genus Here, we describe identification of orthologous sequences in several species belonging to multiple families of rodents outside the genus We show that these orthologs are in the same region of conserved synteny, between the genes and , suggesting a minimum insertion time of 45 million years for the ancient progenitor of Our analysis also revealed that was not detectable or heavily mutated in some lineages in the superfamily , while, in concert with previous findings in the genus , we found strong evidence of positive selection of in the African clade in the subfamily Residues identified as evolving under positive selection include those that have been previously found to be important for restriction of multiple retroviral lineages. Taken together, these findings suggest that the evolutionary origin of substantially predates evolution, that the rodent has been shaped by lineage-specific differential selection pressures, and that has long been evolving under positive selection in the rodent family , supporting a defensive role that significantly antedates exposure to MLVs. Retroviruses have adapted to living in concert with their hosts throughout vertebrate evolution. Over the years, the study of these relationships revealed the presence of host proteins called restriction factors that inhibit retroviral replication in host cells. The first of these restriction factors to be identified, encoded by the gene found in mice, was thought to have originated in the genus In this study, we utilized genome database searches and DNA sequencing to identify copies in multiple rodent lineages. Our findings suggest a minimum time of insertion into the genome of rodents of 45 million years for the ancestral progenitor of While is not detectable in some lineages, we also identified full-length orthologs showing signatures of a molecular "arms race" in a family of rodent species indigenous to Africa. This finding suggests that in these species has been coevolving with unidentified retroviruses for millions of years.
实验室鼠基因编码一种逆转录病毒限制因子，介导对鼠白血病病毒 (MLV) 的抗性。与内源性鼠逆转录病毒 L (MuERV-L) 家族 ERV 的 蛋白的序列相似性表明，是从古老的前病毒中获得的。先前的进化研究仅在属中发现了 的同源物。在这里，我们描述了在属外的多个啮齿动物科的几个物种中鉴定出的 直系同源物。我们表明，这些 直系同源物位于基因 和 之间保守同线性的同一区域，表明古老前体的插入时间至少为 4500 万年。我们的分析还表明，在超家族 中的一些谱系中， 或检测不到或严重突变，而与在属中发现的结果一致，我们发现非洲支系中的 受到强烈的正选择证据，在亚科 中。鉴定为进化受正选择影响的残基包括先前发现对多种逆转录病毒谱系的限制很重要的残基。总之，这些发现表明 的进化起源远早于 的进化，啮齿动物 受到谱系特异性差异选择压力的影响，并且 在啮齿动物科 中一直受到正选择的进化，支持了与 MLV 接触之前就存在的防御作用。逆转录病毒在脊椎动物进化过程中与宿主协同进化。多年来，对这些关系的研究揭示了存在宿主蛋白，称为限制因子，可抑制宿主细胞中的逆转录病毒复制。在这些限制因子中，第一个被鉴定的，由在小鼠中发现的 基因编码，被认为起源于属。在这项研究中，我们利用基因组数据库搜索和 DNA 测序来鉴定多个啮齿动物谱系中的 拷贝。我们的发现表明，对于啮齿动物基因组中的祖先前体，插入时间至少为 4500 万年。虽然在一些谱系中检测不到 ，但我们还鉴定了全长的直系同源物，这些同源物显示了在非洲本土的一个啮齿动物科的分子“军备竞赛”的特征。这一发现表明，在这些物种中， 与未鉴定的逆转录病毒共同进化了数百万年。
