Mutational robustness in ribozyme quasispecies

这项工作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通常会对诱变药物产生耐药性，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表现出的延长灭绝时间的分子基础，在第二个FY期间，我用两种方法完成了适应度值和种群大小的测量，并且为了保守起见，我在删除可能归因于测序错误的单个序列后重新绘制了网络，共同创建了结果。对于诱变治疗，保守网络显示出真实的基因型网络，而对于非诱变治疗，网络的复杂性大大降低。在诱变处理中，基因型复杂性的数量有明显的不同。这是关键，因为诱变剂具有创造进化潜力的潜在影响。这确实是抗病毒治疗的一个问题：不知道到底要加入多少诱变剂。我们还发现了诱变剂的一个重要的混淆效应，它可以帮助解释被诱变的种群的存活（与没有添加诱变剂的种群灭绝相反）。观察到的群体规模效应的增加，可以抵消有害突变积累和/或随机效应造成的规模减少。这些结果具有挑衅性，正在发表过程中。

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.