Institut Cavanilles de Biodiversitat i Biologia Evolutiva and Departamento de Genética, Universitat de València, Spain.
Mol Biol Evol. 2011 Apr;28(4):1333-8. doi: 10.1093/molbev/msq329. Epub 2010 Dec 6.
The genomes of many RNA viruses contain abundant secondary structures that have been shown to be important for understanding the evolution of noncoding regions and synonymous sites. However, the consequences for protein evolution are less well understood. Recently, the secondary structure of the HIV-1 RNA genome has been experimentally determined. Using this information, here we show that RNA structure and proteins do not evolve independently. A negative correlation exists between the extent of base pairing in the genomic RNA and amino acid variability. Relaxed RNA structures may favor the accumulation of genetic variation in proteins and, conversely, sequence changes driven by positive selection at the protein level may disrupt existing RNA structures. We also find that breakage of RNA base pairs might impose a fitness cost to drug resistance mutations in the protease and reverse transcriptase genes, thereby limiting their spread among untreated patients. Characterizing the evolutionary trade-offs between the selective pressures acting at the RNA and protein levels will help us to better understand the variability and evolution of HIV-1.
许多 RNA 病毒的基因组包含丰富的二级结构，这些结构已被证明对理解非编码区域和同义位点的进化很重要。然而，蛋白质进化的后果还不太清楚。最近，HIV-1 RNA 基因组的二级结构已通过实验确定。利用这些信息，我们在这里表明 RNA 结构和蛋白质并非独立进化。基因组 RNA 中的碱基配对程度与氨基酸变异性之间存在负相关关系。RNA 结构的松弛可能有利于蛋白质中遗传变异的积累，相反，由蛋白质水平的正选择驱动的序列变化可能会破坏现有的 RNA 结构。我们还发现，RNA 碱基对的断裂可能会给蛋白酶和逆转录酶基因中的耐药突变带来适应度代价，从而限制它们在未经治疗的患者中的传播。对在 RNA 和蛋白质水平上起作用的选择压力之间的进化权衡进行特征描述，将有助于我们更好地理解 HIV-1 的变异性和进化。
