Department of Organismal Biology, Uppsala University, Norbyvägen 18D, 752 36 Uppsala, Sweden.
Department of Medical Biochemistry and Microbiology, Uppsala University, Husargatan 3, 751 23 Uppsala, Sweden.
Curr Biol. 2019 Aug 19;29(16):2758-2765.e6. doi: 10.1016/j.cub.2019.07.025. Epub 2019 Aug 8.
Most mutations in coding regions of the genome are deleterious, causing selection to favor mechanisms that minimize the mutational load over time [1-5]. DNA replication during cell division is a major source of new mutations. It is therefore important to limit the number of cell divisions between generations, particularly for large and long-lived organisms [6-9]. The germline cells of animals and the slowly dividing cells in plant meristems are adaptations to control the number of mutations that accumulate over generations [9-11]. Fungi lack a separated germline while harboring species with very large and long-lived individuals that appear to maintain highly stable genomes within their mycelia [8, 12, 13]. Here, we studied genomic mutation accumulation in the fairy-ring mushroom Marasmius oreades. We generated a chromosome-level genome assembly using a combination of cutting-edge DNA sequencing technologies and re-sequenced 40 samples originating from six individuals of this fungus. The low number of mutations recovered in the sequencing data suggests the presence of an unknown mechanism that works to maintain extraordinary genome integrity over vegetative growth in M. oreades. The highly structured growth pattern of M. oreades allowed us to estimate the number of cell divisions leading up to each sample [14, 15], and from this data, we infer an incredibly low per mitosis mutation rate (3.8 × 10 mutations per site and cell division) as one of several possible explanations for the low number of identified mutations.
大多数基因组编码区域的突变都是有害的,导致选择有利于随着时间的推移最小化突变负荷的机制[1-5]。细胞分裂过程中的 DNA 复制是新突变的主要来源。因此,重要的是要限制世代之间的细胞分裂次数,特别是对于大型和长寿的生物[6-9]。动物的生殖细胞和植物分生组织中缓慢分裂的细胞是适应控制世代间积累的突变数量的机制[9-11]。真菌缺乏分离的生殖细胞,但却拥有非常大和长寿的物种,这些物种似乎在其菌丝体中保持高度稳定的基因组[8,12,13]。在这里,我们研究了仙女环蘑菇 Marasmius oreades 中的基因组突变积累。我们使用一系列最先进的 DNA 测序技术组合生成了一个染色体水平的基因组组装,并对来自该真菌的六个个体的 40 个样本进行了重测序。测序数据中回收的突变数量很少,这表明存在一种未知的机制,可以在 M.oreades 的营养生长过程中维持非凡的基因组完整性。M.oreades 的高度结构化的生长模式使我们能够估计每个样本之前的细胞分裂次数[14,15],并且根据这些数据,我们推断出每有丝分裂的突变率(每个位点和细胞分裂 3.8×10 个突变)极低,这是识别突变数量较少的几种可能解释之一。