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豚鼠肌球蛋白融合基因的分子特性和进化起源:来自细小病毒的基因。

Molecular Properties and Evolutionary Origins of a Parvovirus-Derived Myosin Fusion Gene in Guinea Pigs.

机构信息

Instituto de Ciencias Biomedicas, Facultad de Medicina, Universidad Andres Bello, Santiago, Chile.

Departamento de Ciencias Biologicas, Facultad de Ciencias de la Vida, Universidad Andres Bello, Viña del Mar, Chile.

出版信息

J Virol. 2019 Aug 13;93(17). doi: 10.1128/JVI.00404-19. Print 2019 Sep 1.

Abstract

Sequences derived from parvoviruses (family ) are relatively common in animal genomes, but the functional significance of these endogenous parvoviral element (EPV) sequences remains unclear. In this study, we used a combination of and molecular biological approaches to investigate a fusion gene carried by guinea pigs (genus ) that is partially derived from an EPV. This gene, named , encodes a predicted polypeptide gene product comprising a partial 9-like () gene fused to a 3' truncated, EPV-encoded replicase. We examined the genomic and phylogenetic characteristics of the EPV locus () that encodes the viral portions of , revealing that it derives from an ancient dependoparvovirus (genus ) that was incorporated into the guinea pig germ line between approximately 22 and 35 million years ago (MYA). Despite these ancient origins, the regions of the locus that are expressed in the gene are conserved across multiple species in the family Caviidae (guinea pigs and cavies), consistent with a potential function at the amino acid level. Using molecular biological approaches, we further demonstrated that (i) mRNA is broadly transcribed in guinea pig cells, (ii) the cloned transcript can express a protein of the expected size in guinea pig cells , and (iii) the expressed protein localizes to the cytosol. Our findings demonstrate that, consistent with a functional role, the fusion gene is evolutionarily conserved, broadly transcribed, and capable of expressing protein. DNA from viruses has been "horizontally transferred" to mammalian genomes during evolution, but the impact of this process on mammalian biology remains poorly understood. The findings of our study indicate that a novel gene has evolved in guinea pigs through fusion of host and virus genes.

摘要

源自细小病毒科(Parvoviridae)的序列在动物基因组中相对常见,但这些内源性细小病毒元件(Endogenous Parvoviral Element,EPV)序列的功能意义仍不清楚。在这项研究中,我们采用组合的和分子生物学方法,研究了一种来自豚鼠(Cavia porcellus)的融合基因,该基因部分源自 EPV。该基因被命名为,编码一个预测的多肽基因产物,由部分 9 样()基因融合到 3' 截断的、EPV 编码的复制酶组成。我们研究了编码病毒部分的 EPV 基因座()的基因组和系统发育特征,揭示它源自一种古老的依赖细小病毒(Dependoparvovirus)(属),大约在 2200 万至 3500 万年前(MYA)整合到豚鼠的种系中。尽管有这些古老的起源,但在家族 Caviidae(豚鼠和豚鼠科)的多个物种中,表达在基因中的 基因座的区域是保守的,这与潜在的氨基酸水平功能一致。使用分子生物学方法,我们进一步证明:(i)在豚鼠细胞中广泛转录;(ii)克隆的 转录本可以在豚鼠细胞中表达预期大小的蛋白;(iii)表达的蛋白定位于细胞质。我们的发现表明,与功能作用一致,融合基因在进化上是保守的,广泛转录,并能够表达蛋白。在进化过程中,病毒 DNA 已经“水平转移”到哺乳动物基因组中,但这一过程对哺乳动物生物学的影响仍知之甚少。我们研究的结果表明,一种新的基因通过宿主和病毒基因的融合在豚鼠中进化而来。

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