Department of Microbiology and Cell Biology, Montana State University, Bozeman, MT 59717, USA.
Basic Sciences Division, Fred Hutchinson Cancer Center, Seattle, WA 98109, USA.
Mol Biol Evol. 2024 Apr 2;41(4). doi: 10.1093/molbev/msae061.
Selfish genetic elements comprise significant fractions of mammalian genomes. In rare instances, host genomes domesticate segments of these elements for function. Using a complete human genome assembly and 25 additional vertebrate genomes, we re-analyzed the evolutionary trajectories and functional potential of capsid (CA) genes domesticated from Metaviridae, a lineage of retrovirus-like retrotransposons. Our study expands on previous analyses to unearth several new insights about the evolutionary histories of these ancient genes. We find that at least five independent domestication events occurred from diverse Metaviridae, giving rise to three universally retained single-copy genes evolving under purifying selection and two gene families unique to placental mammals, with multiple members showing evidence of rapid evolution. In the SIRH/RTL family, we find diverse amino-terminal domains, widespread loss of protein-coding capacity in RTL10 despite its retention in several mammalian lineages, and differential utilization of an ancient programmed ribosomal frameshift in RTL3 between the domesticated CA and protease domains. Our analyses also reveal that most members of the PNMA family in mammalian genomes encode a conserved putative amino-terminal RNA-binding domain (RBD) both adjoining and independent from domesticated CA domains. Our analyses lead to a significant correction of previous annotations of the essential CCDC8 gene. We show that this putative RBD is also present in several extant Metaviridae, revealing a novel protein domain configuration in retrotransposons. Collectively, our study reveals the divergent outcomes of multiple domestication events from diverse Metaviridae in the common ancestor of placental mammals.
自私的遗传元件构成了哺乳动物基因组的重要部分。在极少数情况下，宿主基因组会驯化这些元件的某些片段以发挥功能。利用完整的人类基因组组装和 25 个额外的脊椎动物基因组，我们重新分析了从 Metaviridae 驯化的衣壳 (CA) 基因的进化轨迹和功能潜力，Metaviridae 是一类类似于逆转录病毒的逆转录转座子。我们的研究扩展了以前的分析，揭示了这些古老基因进化历史的一些新见解。我们发现，至少有五个独立的驯化事件来自不同的 Metaviridae，产生了三个普遍保留的单拷贝基因，在净化选择下进化，还有两个基因家族是胎盘哺乳动物所特有的，其中多个成员显示出快速进化的证据。在 SIRH/RTL 家族中，我们发现了多样化的氨基末端结构域，尽管 RTL10 在几个哺乳动物谱系中保留了下来，但它的编码能力广泛丧失，而且在驯化的 CA 和蛋白酶结构域之间，RTL3 中古老的程序性核糖体移码存在差异。我们的分析还表明，哺乳动物基因组中 PNMA 家族的大多数成员编码一个保守的假定氨基末端 RNA 结合域 (RBD)，该域与驯化的 CA 结构域毗邻或独立。我们的分析导致了对以前关于重要 CCDC8 基因注释的重大修正。我们表明，这个假定的 RBD 也存在于几种现存的 Metaviridae 中，揭示了逆转录转座子中一种新的蛋白质结构域配置。总之，我们的研究揭示了胎盘哺乳动物共同祖先中来自不同 Metaviridae 的多个驯化事件的不同结果。
