Data from: Regular bottlenecks and restrictions to somatic fusion prevent the accumulation of mitochondrial defects in Neurospora

The replication and segregation of the multi-copy mitochondrial DNA (mtDNA) are not under strict control of the nuclear DNA. Within-cell selection may thus favour variants with an intracellular selective advantage but a detrimental effect on cell fitness. High relatedness among the mtDNA variants of an individual is predicted to disfavour such deleterious selfish genetic elements, but experimental evidence for this hypothesis is scarce. We studied the effect of mtDNA relatedness on the opportunities for suppressive mtDNA variants in the fungus Neurospora carrying the mitochondrial mutator plasmid pKALILO (pKAL). During growth, this plasmid integrates into the mitochondrial genome, generating suppressive mtDNA variants. These mtDNA variants gradually replace the wild-type mtDNA, ultimately culminating in growth arrest and death. We show that regular sequestration of mtDNA variation is required for effective selection against suppressive mtDNA variants. First, bottlenecks in the number of mtDNA copies from which a ‘Kalilo’ culture started significantly increased the maximum lifespan and variation in life span among cultures. Second, restrictions to somatic fusion among fungal individuals, either by using anastomosis-deficient mutants or by generating allotype diversity, prevented the accumulation of suppressive mtDNA variants. We discuss the implications of these results for the somatic accumulation of mitochondrial defects during ageing.

多拷贝线粒体DNA（mtDNA）的复制与分离并不受核DNA的严格调控。因此，细胞内的选择可能会青睐那些具备细胞内选择优势，但却对细胞适合度产生有害影响的变异体。理论预测，个体内线粒体DNA变异体间的高度亲缘性会抑制这类有害自私遗传因子的增殖，但验证该假说的实验证据却十分匮乏。我们以携带线粒体突变体质粒pKALILO（pKAL）的脉孢霉（Neurospora）为实验材料，探究了线粒体DNA亲缘性对抑制型线粒体DNA变异体增殖机会的影响。在培养生长过程中，该质粒会整合进入线粒体基因组，进而产生抑制型线粒体DNA变异体。这类变异体会逐步取代野生型线粒体DNA，最终导致生长停滞与个体死亡。我们的研究证实，对线粒体DNA变异进行定期隔离是有效抑制抑制型线粒体DNA变异体的必要前提。其一，以少量线粒体DNA拷贝为起始建立的"Kalilo"培养物，其最长存活时间与存活时长的个体差异均显著升高。其二，通过使用菌丝融合缺陷突变体或构建同种异型多样性来限制真菌个体间的体细胞融合，可有效阻断抑制型线粒体DNA变异体的积累。我们还就上述结果对于衰老过程中线粒体缺陷的体细胞积累的研究意义展开了讨论。