Viruses are under constant evolutionary pressure to effectively interact with the host intracellular factors, while evading its immune system. Understanding how viruses co-evolve with their hosts is a fundamental topic in molecular evolution and may also aid in developing novel viral based applications such as vaccines, oncologic therapies, and anti-bacterial treatments. Here, based on a novel statistical framework and a large-scale genomic analysis of 2,625 viruses from all classes infecting 439 host organisms from all kingdoms of life, we identify short nucleotide sequences that are under-represented in the coding regions of viruses and their hosts. These sequences cannot be explained by the coding regions' amino acid content, codon, and dinucleotide frequencies. We specifically show that short homooligonucleotide and palindromic sequences tend to be under-represented in many viruses probably due to their effect on gene expression regulation and the interaction with the host immune system. In addition, we show that more sequences tend to be under-represented in dsDNA viruses than in other viral groups. Finally, we demonstrate, based on in vitro and in vivo experiments, how under-represented sequences can be used to attenuated Zika virus strains.

中文翻译：

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针对病毒及其相关宿主中短核苷酸序列的进化选择。

病毒处于不断的进化压力下，以有效地与宿主细胞内因子相互作用，同时逃避其免疫系统。了解病毒如何与其宿主共同进化是分子进化的一个基本主题，也可能有助于开发基于病毒的新型应用，例如疫苗、肿瘤疗法和抗菌疗法。在这里，基于新的统计框架和对感染所有生命界的 439 种宿主生物的所有类别的 2,625 种病毒的大规模基因组分析，我们确定了在病毒及其宿主的编码区中代表性不足的短核苷酸序列. 这些序列不能用编码区的氨基酸含量、密码子和二核苷酸频率来解释。我们特别表明，短同源寡核苷酸和回文序列在许多病毒中的代表性不足，这可能是由于它们对基因表达调控和与宿主免疫系统相互作用的影响。此外，我们表明，与其他病毒组相比，更多的序列在 dsDNA 病毒中的代表性不足。最后，我们基于体外和体内实验证明了代表性不足的序列如何用于减毒寨卡病毒株。