Endogenous retroviruses (ERVs) are remnants of ancient retroviral infections of mammalian germline cells. A large proportion of ERVs lose their open reading frames (ORFs), while others retain them and become exapted by the host species. However, it remains unclear what proportion of ERVs possess ORFs (ERV-ORFs), become transcribed, and serve as candidates for co-opted genes. We investigated characteristics of 176,401 ERV-ORFs containing retroviral-like protein domains (gag, pro, pol, and env) in 19 mammalian genomes. The fractions of ERVs possessing ORFs were overall small (~ 0.15%) although they varied depending on domain types as well as species. The observed divergence of ERV-ORF from their consensus sequences showed bimodal distributions, suggesting that a large proportion of ERV-ORFs either recently, or anciently, inserted themselves into mammalian genomes. Alternatively, very few ERVs lacking ORFs were found to exhibit similar divergence patterns. To identify candidates for ERV-derived genes, we estimated the ratio of non-synonymous to synonymous substitution rates (dN/dS) for ERV-ORFs in human and non-human mammalian pairs, and found that approximately 42% of the ERV-ORFs showed dN/dS < 1. Further, using functional genomics data including transcriptome sequencing, we determined that approximately 9.7% of these selected ERV-ORFs exhibited transcriptional potential. These results suggest that purifying selection operates on a certain portion of ERV-ORFs, some of which may correspond to uncharacterized functional genes hidden within mammalian genomes. Together, our analyses suggest that more ERV-ORFs may be co-opted in a host-species specific manner than we currently know, which are likely to have contributed to mammalian evolution and diversification.

中文翻译：

---

综合基因组分析揭示了编码逆转录病毒样蛋白结构域的内源逆转录病毒的动态进化。

内源性逆转录病毒 (ERV) 是哺乳动物生殖细胞的古代逆转录病毒感染的残余物。大部分 ERV 失去了它们的开放阅读框 (ORF)，而另一些则保留了它们并被宿主物种扩展。然而，目前尚不清楚有多少比例的 ERVs 拥有 ORFs (ERV-ORFs)，被转录，并作为增选基因的候选者。我们调查了 19 个哺乳动物基因组中 176,401 个含有逆转录病毒样蛋白结构域（gag、pro、pol 和 env）的 ERV-ORF 的特征。拥有 ORF 的 ERV 的比例总体上很小（~0.15%），尽管它们因域类型和物种而异。观察到的 ERV-ORF 与其共有序列的差异显示出双峰分布，这表明大部分 ERV-ORF 最近或古代，将自己插入哺乳动物基因组。或者，发现很少有缺乏 ORF 的 ERV 表现出类似的分歧模式。为了确定 ERV 衍生基因的候选者，我们估计了人类和非人类哺乳动物对中 ERV-ORF 的非同义替换率 (dN/dS)，发现大约 42% 的 ERV-ORF显示 dN/dS < 1。此外，使用包括转录组测序在内的功能基因组学数据，我们确定这些选定的 ERV-ORF 中约有 9.7% 表现出转录潜力。这些结果表明纯化选择作用于 ERV-ORF 的特定部分，其中一些可能对应于隐藏在哺乳动物基因组中的未表征的功能基因。一起，