Repeat-induced point (RIP) mutation in Neurospora crassa degrades transposable elements by targeting repeats with C→T mutations. Whether RIP affects core genomic sequence in important ways is unknown. By parent-offspring whole genome sequencing, we estimate a mutation rate (3.38 × 10−6 per bp per generation) that is two orders of magnitude higher than reported for any non-viral organism, with 93–98% of mutations being RIP-associated. RIP mutations are, however, relatively rare in coding sequence, in part because RIP preferentially attacks GC-poor long duplicates that interact in three dimensional space, while coding sequence duplicates are rare, GC-rich, short, and tend not to interact. Despite this, with over 5 coding sequence mutations per genome per generation, the mutational burden is an order of magnitude higher than the previously highest observed. Unexpectedly, the majority of these coding sequence mutations appear not to be the direct product of RIP being mostly in non-duplicate sequence and predominantly not C→T mutations. Nonetheless, RIP-deficient strains have over an order of magnitude fewer coding sequence mutations outside of duplicated domains than RIP-proficient strains. Neurospora crassa has the highest mutation rate and mutational burden of any non-viral life. While the high rate is largely due to the action of RIP, the mutational burden appears to be RIP-associated but not directly caused by RIP.

中文翻译：

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粗糙脉孢菌中重复诱导的点突变导致已知的最高突变率和任何细胞生命的突变负担

粗糙脉孢菌中的重复诱导点 (RIP) 突变通过靶向具有 C→T 突变的重复序列来降解转座因子。RIP 是否以重要方式影响核心基因组序列尚不清楚。通过亲代全基因组测序，我们估计突变率（每 bp 每代 3.38 × 10−6）比报告的任何非病毒生物高两个数量级，其中 93-98% 的突变是 RIP-联系。然而，RIP 突变在编码序列中相对罕见，部分原因是 RIP 优先攻击在 3 维空间中相互作用的 GC 贫乏的长重复序列，而编码序列重复序列很少，富含 GC，并且往往不相互作用。尽管如此，每代每个基因组有超过 5 个编码序列突变，突变负担比之前观察到的最高值高一个数量级。出乎意料的是，这些编码序列突变中的大多数似乎不是 RIP 的直接产物，主要是非重复序列，主要不是 C→T 突变。尽管如此，RIP 缺陷菌株的重复域之外的编码序列突变比 RIP 熟练菌株少一个数量级。粗糙脉孢菌的突变率和突变负荷是所有非病毒生命中最高的。虽然高比率主要是由于 RIP 的作用，但突变负担似乎与 RIP 相关，但不是由 RIP 直接引起的。尽管如此，RIP 缺陷菌株的重复域之外的编码序列突变比 RIP 熟练菌株少一个数量级。粗糙脉孢菌的突变率和突变负荷是所有非病毒生命中最高的。虽然高比率主要是由于 RIP 的作用，但突变负担似乎与 RIP 相关，但不是由 RIP 直接引起的。尽管如此，RIP 缺陷菌株的重复域之外的编码序列突变比 RIP 熟练菌株少一个数量级。粗糙脉孢菌的突变率和突变负荷是所有非病毒生命中最高的。虽然高比率主要是由于 RIP 的作用，但突变负担似乎与 RIP 相关，但不是由 RIP 直接引起的。