COMPUTER-ASSISTED STUDY OF FUNCTIONS AND EVOLUTION OF LARGE DNA VIRUS GENOMES

蛋白质氨基酸序列的计算机辅助比对 彼此之间以及与相关细胞蛋白相互作用的大型DNA病毒 执行，重点是可能特定影响的蛋白质 病毒的毒性。大型DNA病毒基因序列的海量集合 包括一个完整的痘病毒基因组和 几个疱疹病毒基因组。很大一部分的功能 这些病毒编码的蛋白质尚不清楚。特别的 令人感兴趣的是对病毒在组织中的生长不是必需的基因 培养，但影响病毒的毒力。痘病毒蛋白家族是 描述了包含两个明显类似于 无关的细胞蛋白质。N端结构域涉及 几个转录因子的相似位置的结构域，以及 C末端结构域类似于小鼠胎盘特异性蛋白MIPP。 后一个结构域由四个或五个不完全重复组成的阵列组成。 我们的分析也揭示了这个蛋白质家族的截短成员 痘病毒，暗示了一条复杂的进化途径，可能 涉及复制和删除。几种病毒的功能 预测了利用NTP的酶，包括两个痘病毒解旋酶 和一个可能参与病毒成熟的假定的NTPase。一个 在与哺乳动物有关的鸡痘病毒中发现了蛋白质 胞苷酸激酶，并被认为具有相同的酶活性。 病毒和细胞性胸腺嘧啶核苷和胸腺嘧啶核苷的初步系统发育 产生了激酶，并提出了一种假说，即基因编码 因为核苷酸代谢的酶可以通过以下方式独立获得 不同的病毒通过与各自的细胞基因重组。 在一种编码的蛋白质中发现了锌指基序的一个特定版本 由鼠痘病毒的一个基因所致，该基因已在中国科学院实验室测序 病毒性疾病，并已被证明是病毒的关键 对它的自然宿主来说是致命的。锌指的比较分析 各个家族的蛋白质都在研究中。

Computer-assisted comparisons of amino acid sequences of proteins of large DNA viruses with each other and with related cellular proteins were performed, with the emphasis on proteins that may specifically influence virus virulence. Vast collections of gene sequences of large DNA viruses are currently available, including one complete poxvirus genome and several herpesvirus genomes. The functions of a large fraction of proteins encoded by these viruses are not understood. Of particular interest are genes that are not essential for virus growth in tissue culture but influence virus virulence. A family of poxvirus proteins was described that contain two distinct domains similar to apparently unrelated cellular proteins. The N-terminal domain is related to similarly located domains of several transcription factors, and the C-terminal domain resembles a murine placental-specific protein MIPP. The latter domain consists of an array of four or five imperfect repeats. Our analysis revealed also truncated members of this protein family in poxviruses, suggesting a complex evolutionary pathway that might have involved duplications and deletions. Functions of several viral NTP-utilizing enzymes were predicted, including two poxvirus helicases and a putative NTPase that may be involved in virus maturation. A protein was identified in fowlpox virus that is related to mammalian cytidylate kinase and is proposed to possess the same enzymatic activity. A tentative phylogeny of viral and cellular thymidine and thymidylate kinases was generated and a hypothesis was developed that genes coding for enzymes of nucleotide metabolism could be acquired independently by different viruses via recombination with the respective cellular genes. A specific version of Zn finger motif was identified in a protein encoded by a gene of mousepox virus that has been sequenced in the Laboratory of Viral Diseases and has been shown to be essential for the virus to be virulent for its natural host. The comparative analysis of the Zn finger proteins of the respective family is in progress.