Abstract Herpesviruses (HVs, Family: Herpesviridae) have large genomes that encode hundreds of proteins. Apart from amino acid mutations, protein domain acquisitions, duplications and losses are also common modes of evolution. HV domain repertoires differ across species, and only a core set is shared among all species, aspect that raises a question: How have HV domain repertoires diverged while keeping some similarities? To answer such question, we used profile Hidden Markov Models (HMMs) to search for domains in all possible translated open reading frames (ORFs) of fully sequenced HV genomes. With at least 274 domains being identified, we built a matrix of domain counts per species, and applied a parsimony method to reconstruct the ancestral states of these domains along the HV phylogeny. It revealed events of domain gain, duplication, and loss over more than 400 millions of years, where Alpha-, Beta-, and GammaHVs expanded and condensed their domain repertoires at distinct rates. Most of the acquired domains perform ‘Modulation and Control’, ‘Envelope’, or ‘Auxiliary’ functions, categories that showed high flexibility (number of domains) and redundancy (number of copies). Conversely, few gains and duplications were observed for domains involved in ‘Capsid assembly and structure’, and ‘DNA Replication, recombination and metabolism’. Among the forty-one primordial domains encoded by Herpesviridae ancestors, twenty-eight are still found in all present-day HVs. Because of their distinct evolutionary strategies, HV domain repertoires are very specific at the subfamily, genus and species levels. Differences in domain composition may not only explain HV host range and tissue tropism, but also provide hints to the origins of HVs.

中文翻译：

---

蛋白质域库的进化：揭示疱疹病毒科的起源

摘要 疱疹病毒（HVs，Family：Herpesviridae）具有编码数百种蛋白质的大型基因组。除了氨基酸突变，蛋白质结构域的获得、复制和丢失也是常见的进化模式。HV 域库因物种而异，并且只有一个核心集在所有物种之间共享，这一方面提出了一个问题：HV 域库如何在保持一些相似性的同时发生分歧？为了回答这个问题，我们使用了隐马尔可夫模型 (HMM) 来搜索完全测序的 HV 基因组的所有可能的翻译开放阅读框 (ORF) 中的域。确定了至少 274 个域，我们构建了每个物种的域计数矩阵，并应用简约方法沿 HV 系统发育重建这些域的祖先状态。它揭示了域增益、复制、和损失超过 4 亿年，其中 Alpha、Beta 和 GammaHV 以不同的速度扩展和浓缩了他们的领域库。大多数获得的域执行“调制和控制”、“包络”或“辅助”功能，这些类别显示出高度的灵活性（域数）和冗余（副本数）。相反，对于涉及“衣壳组装和结构”以及“DNA 复制、重组和代谢”的域，几乎没有观察到增益和重复。在疱疹病毒科祖先编码的 41 个原始域中，28 个仍存在于所有现代 HV 中。由于其独特的进化策略，HV 域库在亚科、属和种水平上非常具体。域组成的差异不仅可以解释 HV 宿主范围和组织趋向性，