PDF(Pubmed)
Abstract：
Each new human has an expected Ud = 2 - 10 new deleterious mutations. This deluge of deleterious mutations cannot all be purged, and therefore accumulate in a declining fitness ratchet. Using a novel simulation framework designed to efficiently handle genome-wide linkage disequilibria across many segregating sites, we find that rarer, beneficial mutations of larger effect are sufficient to compensate fitness declines due to the fixation of many slightly deleterious mutations. Drift barrier theory posits a similar asymmetric pattern of fixations to explain ratcheting genome size and complexity, but in our theory, the cause is Ud > 1 rather than small population size. In our simulations, Ud ~2 - 10 generates high within-population variance in relative fitness; two individuals will typically differ in fitness by 15-40%. Ud ~2 - 10 also slows net adaptation by ~13%-39%. Surprisingly, fixation rates are more sensitive to changes in the beneficial than the deleterious mutation rate, e.g. a 10% increase in overall mutation rate leads to faster adaptation; this puts to rest dysgenic fears about increasing mutation rates due to rising paternal age.
摘要：
每个新的人都有一个预期的Ud=2-10个新的有害突变。大量的有害突变不能全部清除，因此积累在一个下降的健身棘轮。使用一种新颖的模拟框架，旨在有效地处理跨许多分离位点的全基因组连锁不平衡，我们发现这种情况更罕见，具有较大效应的有益突变足以补偿由于许多轻微有害突变的固定而导致的适应性下降。漂移屏障理论提出了类似的非对称固定模式来解释棘轮基因组大小和复杂性，但在我们的理论中,原因是Ud>1，而不是人口规模较小。在我们的模拟中,Ud~2-10在相对适合度方面产生了很高的群体内方差；两个个体的适合度通常会相差15-40%。Ud~2-10也使净适应速度下降了13%-39%。令人惊讶的是,固定率对有益突变率的变化比有害突变率更敏感，例如，总体突变率增加10％会导致更快的适应；这使人们对由于父辈年龄的增加而导致突变率增加的恐惧得以缓解。
