Graduate School of Information Science and Technology, Hokkaido University, Sapporo 060-0814, Japan.
Department of Ophthalmology, Hokkaido University Graduate School of Medicine, Sapporo 060-8638, Japan.
Gene. 2014 Aug 15;547(1):10-7. doi: 10.1016/j.gene.2014.04.018. Epub 2014 Apr 12.
Human adenovirus species D (HAdV-D), which is composed of clinically and epidemiologically important pathogens worldwide, contains more taxonomic "types" than any other species of the genus Mastadenovirus, although the mechanisms accounting for the high level of diversity remain to be disclosed. Recent studies of known and new types of HAdV-D have indicated that intertypic recombination between distant types contributes to the increasing diversity of the species. However, such findings raise the question as to how homologous recombination events occur between diversified types since homologous recombination is suppressed as nucleotide sequences diverge. In order to address this question, we investigated the distribution of the recombination boundaries in comparison with the landscape of intergenomic sequence conservation assessed according to the synonymous substitution rate (dS). The results revealed that specific genomic segments are conserved between even the most distantly related genomes; we call these segments "universally conserved segments" (UCSs). These findings suggest that UCSs facilitate homologous recombination, resulting in intergenomic segmental exchanges of UCS-flanking genomic regions as recombination modules. With the aid of such a mechanism, the haploid genomes of HAdV-Ds may have been reshuffled, resulting in chimeric genomes out of diversified repertoires in the HAdV-D population analogous to the MHC region reshuffled via crossing over in vertebrates. In addition, some HAdVs with chimeric genomes may have had the opportunity to avoid host immune responses thereby causing epidemics.
人类腺病毒 D 型（HAdV-D）由全球具有临床和流行病学意义的病原体组成，包含的分类“型”比属内其他任何一种巨细胞病毒都多，尽管导致高度多样性的机制仍有待揭示。对已知和新型 HAdV-D 的研究表明，不同型之间的间型重组有助于该物种的多样性增加。然而，这些发现提出了一个问题，即如何在多样化的类型之间发生同源重组事件，因为随着核苷酸序列的分化，同源重组受到抑制。为了解决这个问题，我们研究了重组边界的分布情况，并与根据同义替代率（dS）评估的基因组间序列保守性景观进行了比较。结果表明，即使是亲缘关系最远的基因组之间也存在特定的基因组片段保守；我们将这些片段称为“普遍保守片段”（UCS）。这些发现表明，UCS 促进了同源重组，导致重组模块中 UCS 侧翼基因组区域的基因组片段间交换。借助这种机制，HAdV-D 的单倍体基因组可能已经被重新洗牌，导致 HAdV-D 群体中的多样化基因库中出现嵌合基因组，类似于脊椎动物中通过交叉重组重新洗牌的 MHC 区域。此外，一些具有嵌合基因组的 HAdV 可能有机会逃避宿主的免疫反应，从而引发流行。
