Comprehensive genomic analysis reveals dynamic evolution of mammalian transposable elements that code for viral-like protein domains
Comprehensive genomic analysis reveals dynamic evolution of mammalian transposable elements that code for viral-like protein domains
复制标题
全面的基因组分析揭示了编码病毒样蛋白结构域的哺乳动物转座元件的动态进化
DOI：
10.1101/628875
复制
发表时间：
2019
期刊：
影响因子：
--
通讯作者：
So Nakagawa
中科院分区：
文献类型：
--
作者：
Mahoko T. Ueda;Kirill Kryukov;Satomi Mitsuhashi; Hiroaki Mitsuhashi; Tadashi Imanishi; So Nakagawa
内源性逆转录病毒的转座元件和长散布的核元件编码病毒样蛋白结构域，称为内源性病毒元件（EVE）。很大一部分 EVE 失去了开放阅读框（ORF），而有些则保留了开放阅读框并已被宿主物种所适应。然而，目前尚不清楚拥有 ORF 的 EVE（EVE-ORF）是如何进化并在此过程中开发新功能的。为了解决这些问题，我们检查了 19 个哺乳动物基因组，并研究了大约 600,000 个 EVE-ORF 的特征，其中包含病毒样蛋白结构域的高质量注释。观察到的 EVE 与其共有序列的差异表明，大量的 EVE-ORF 在最近或古代将自身插入到哺乳动物基因组中。另外，很少有缺乏 ORF 的 EVE 被发现表现出类似的分歧模式。此外，EVE-ORF 被确定在转录起始位点和 DNase I 超敏感位点下游的丰度较低，这与缺乏 ORF 的 EVE 形成对比，表明纯化选择过程可能有助于抑制 EVE-ORF 的意外表达。尽管进行了这些观察，我们还是在人类和小鼠 RNA 测序数据中鉴定出了 1,000 多个 EVE-ORF。这表明有可能识别和表达隐藏在哺乳动物基因组中的未表征的 EVE-ORF，其中大多数已被证实具有谱系特异性。我们还证明，每个 EVE-ORF 编码的病毒样蛋白结构域的分数在哺乳动物谱系之间存在差异。总之，我们的分析表明，EVE-ORF（其中许多尚未被发现）可能以宿主物种特定的方式被增选，并且可能对哺乳动物的进化和多样化做出了贡献。 意义声明转座元件（TE），即跳跃基因，占据了哺乳动物基因组的 70%。最近，据报道，编码病毒样蛋白结构域的 TE 在进化过程中获得了新的功能。然而，目前尚不清楚这些拥有开放阅读框（ORF）的TE是如何进化的，同时在其宿主物种内获得新功能。我们发现 19 种哺乳动物中每个病毒样蛋白结构域的片段各不相同。此外，通过对人类和小鼠的表达分析，检测到超过 1000 个 TE 作为转录本。这些结果表明，许多新发现的拥有 ORF 的哺乳动物 TE 可能以谱系特异性方式被增选，并有助于哺乳动物的多样化。
Transposable elements of endogenous retroviruses and long interspersed nuclear elements code for viral-like protein domains, called endogenous viral elements (EVEs). A large proportion of EVEs lose their open reading frames (ORFs), while some maintain them and have been exapted by the host species. However, it remains unclear how ORF-possessing EVEs (EVE-ORFs) have evolved while developing new functions in the process. To address these issues, we examined 19 mammalian genomes and investigated characteristics of approximately 600,000 EVE-ORFs containing high-quality annotations of viral-like protein domains. The observed divergence of EVEs from their consensus sequences suggested that a large number of EVE-ORFs either recently, or anciently, inserted themselves into mammalian genomes. Alternatively, very few EVEs lacking ORFs, were found to exhibit similar divergence patterns. In addition, the EVE-ORFs were determined to be less abundant downstream of transcription initiation sites, and DNase I hypersensitive sites, which was in contrast to EVEs lacking ORFs, indicating that the purifying selection process may serve to suppress unexpected expression of EVE-ORFs. In spite of such observations, we identified more than 1,000 EVE-ORFs in human and mouse RNA-sequencing data. This suggested a possibility to identify and express uncharacterized EVE-ORFs hidden within mammalian genomes, most of which have been confirmed to be lineage specific. We also demonstrated that fractions of each EVE-ORF-encoded viral-like protein domain varied among mammalian lineages. Together, our analyses suggest that EVE-ORFs, many of which have not uncovered yet, may be co-opted in a host-species specific manner and are likely to have contributed to mammalian evolution and diversification.Significance StatementTransposable elements (TEs), known as jumping genes, occupy up to 70% of mammalian genomes. Recently, TEs encoding viral-like protein domains have been reported to have acquired new functions during evolution. However, it is unclear how these TEs possessing open reading frames (ORFs) have evolved while simultaneously obtaining new functions within their host species. We discovered that segments of each viral-like protein domain varied among 19 mammalian species. Furthermore, through expression analysis in humans and mice, more than 1000 TEs were detected as transcripts. These results suggest that many newly identified mammalian TEs possessing ORFs, may have been co-opted in a lineage-specific manner, and served to contribute to mammalian diversification.