Takeuchi Yasuhiro, Myers Richard, Danos Olivier
Medical Reserach Council (MRC)/UCL Centre for Medical Molecular Virology, Division of Infection and Immunology, University College London, London, United Kingdom.
PLoS One. 2008 Feb 20;3(2):e1634. doi: 10.1371/journal.pone.0001634.
Homologous recombination is a dominant force in evolution and results in genetic mosaics. To detect evidence of recombination events and assess the biological significance of genetic mosaics, genome sequences for various viral populations of reasonably large size are now available in the GenBank. We studied a multi-functional viral gene, the adeno-associated virus (AAV) cap gene, which codes for three capsid proteins, VP1, VP2 and VP3. VP1-3 share a common C-terminal domain corresponding to VP3, which forms the viral core structure, while the VP1 unique N-terminal part contains an enzymatic domain with phospholipase A2 activity. Our recombinant detection program (RecI) revealed five novel recombination events, four of which have their cross-over points in the N-terminal, VP1 and VP2 unique region. Comparison of phylogenetic trees for different cap gene regions confirmed discordant phylogenies for the recombinant sequences. Furthermore, differences in the phylogenetic tree structures for the VP1 unique (VP1u) region and the rest of cap highlighted the mosaic nature of cap gene in the AAV population: two dominant forms of VP1u sequences were identified and these forms are linked to diverse sequences in the rest of cap gene. This observation together with the finding of frequent recombination in the VP1 and 2 unique regions suggests that this region is a recombination hot spot. Recombination events in this region preserve protein blocks of distinctive functions and contribute to convergence in VP1u and divergence of the rest of cap. Additionally the possible biological significance of two dominant VP1u forms is inferred.
同源重组是进化中的主导力量，并导致基因镶嵌体的产生。为了检测重组事件的证据并评估基因镶嵌体的生物学意义，GenBank中现已提供各种相当大尺寸病毒群体的基因组序列。我们研究了一种多功能病毒基因，腺相关病毒（AAV）的衣壳蛋白基因（cap基因），它编码三种衣壳蛋白VP1、VP2和VP3。VP1 - 3共享一个对应于VP3的共同C末端结构域，VP3形成病毒核心结构，而VP1独特的N末端部分包含一个具有磷脂酶A2活性的酶结构域。我们的重组检测程序（RecI）揭示了五个新的重组事件，其中四个在N末端、VP1和VP2独特区域有交叉点。不同cap基因区域的系统发育树比较证实了重组序列的不一致系统发育。此外，VP1独特区域（VP1u）和cap基因其余部分的系统发育树结构差异突出了AAV群体中cap基因的镶嵌性质：鉴定出两种主要形式的VP1u序列，并且这些形式与cap基因其余部分的不同序列相关联。这一观察结果以及在VP1和VP2独特区域频繁重组的发现表明该区域是一个重组热点。该区域的重组事件保留了具有独特功能的蛋白模块，并导致VP1u中的趋同和cap基因其余部分的分化。此外，还推断了两种主要VP1u形式可能的生物学意义。
