Mutational robustness in ribozyme quasispecies

本研究的目的是为了更好地理解为什么在诱变压力下的病毒种群往往会对诱变药物产生抗性，从而使抗病毒治疗无效。为了更好地理解在诱变环境压力下进化的种群所表现出的延长的灭绝时间的分子基础，在第二个财政年度，我完成了用两种方法测量适应度值、种群大小、保守的网络显示了诱变处理的真实的基因型网络，而对于非诱变处理，网络的复杂性大大降低。在诱变处理中，基因型复杂性的积累量存在明显差异。这是关键，因为诱变剂具有创造进化潜力的潜在作用。这确实是抗病毒治疗的一个问题：不知道到底要添加多少诱变剂。我们还发现了所用诱变剂的一个重要混淆效应，这有助于解释诱变种群的存活（与未添加诱变剂的种群灭绝相反）。观察到的群体大小效应的增加可以抵消由有害突变和/或随机效应的积累引起的大小减小。这些结果具有启发性，正在出版过程中。

The aim of the work is to better understand why viral populations under mutagenic pressures can often develop resistant to mutagenic drugs rendering antiviral treatments ineffective.To better understand the molecular underpinning of the extended time to extinction exhibited by populations evolving under mutagenized environmental pressure, during the second FY, I finished measuring fitness values, population sizes with two methods, and to be conservative I redraw the networks after removing single sequences potentially attributable to sequencing errors, cofounding the results.The conservative networks show real genotypic networks for mutagenic treatments, while for the non-mutagenic treatment the complexity of the network largely dropped. There is a clear difference in the amount of genotypic complexity build up in mutagenic treatments. This is key because mutagens have the potential effect of creating evolutionary potential. It is indeed a problem with antiviral therapies: not knowing exactly how much mutagen to add.We also found an important confounding effect of the mutagen used that can help explain the survival of the mutagenized populations (opposite to populations with no mutagen added that went extinct). The increase in population size effect observed, can counteract decreases in size caused by the accumulation of deleterious mutations and/or stochastic effects. These results are provocative and are in process of publication.