The conflict within: origin, proliferation and persistence of a spontaneously arising selfish mitochondrial genome
The conflict within: origin, proliferation and persistence of a spontaneously arising selfish mitochondrial genome
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DOI：
10.1098/rstb.2019.0174
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发表时间：
2020-01-20
影响因子：
6.3
通讯作者：
Bergthorsson, Ulfar
中科院分区：
文献类型：
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作者：
Dubie, Joseph James;Caraway, Avery Robert;Bergthorsson, Ulfar
线粒体基因组可以维持突变，同时对个体适应性有害，但由于复制优势，可以在个体内增殖。我们分析了秀丽隐杆线虫中编码复合体III的细胞色素B的细胞色素B（1）（ct B-1）基因（Delta ct B-1）中含有新的499 bp缺失的线粒体基因组的适应性效应和种群动力学。在突变累积实验期间，Delta ctb-1在一个实验品系中达到96%的高异质性频率，并且与nd 5和tRNA-Asn中的额外自发突变相关。相对于携带野生型（WT）线粒体的个体，Delta ctb-1突变体线粒体型造成了显着的适应性成本，包括生产力和竞争适应性分别降低65%和52%。在实验种群中，当与携带WT线粒体DNA（mtDNA）的蠕虫竞争时，携带缺失的蠕虫在几代内被迅速清除。相比之下，三角洲ctb-1的有丝分裂型是能够坚持在大的人口包括异质性的个人，虽然三角洲ctb-1的平均细胞内频率表现出缓慢下降，由于个人之间的竞争轴承不同频率的异质性。在经历严重群体瓶颈的实验品系（n = 1）内，Delta ctb-1的相对细胞内频率增加，这是自私驱动的标志。Delta ctb-1和WT mtDNA拷贝数之间的正相关表明了一种增加总mtDNA本身的机制，并且不能区分Delta ctb-1和WT mtDNA。这项研究证明了自私的性质的三角洲ctb-1的有丝分裂型，其传输优势和大量的健身负荷的主机，并强调了人口规模的重要性，自私的mtDNA的人口动态。这篇文章是主题问题“连接线粒体基因型表型：一个复杂的努力”的一部分。
Mitochondrial genomes can sustain mutations that are simultaneously detrimental to individual fitness and yet, can proliferate within individuals owing to a replicative advantage. We analysed the fitness effects and population dynamics of a mitochondrial genome containing a novel 499 bp deletion in the cytochrome b(1) (ctb-1) gene (Delta ctb-1) encoding the cytochrome b of complex III in Caenorhabditis elegans. Delta ctb-1 reached a high heteroplasmic frequency of 96% in one experimental line during a mutation accumulation experiment and was linked to additional spontaneous mutations in nd5 and tRNA-Asn. The Delta ctb-1 mutant mitotype imposed a significant fitness cost including a 65% and 52% reduction in productivity and competitive fitness, respectively, relative to individuals bearing wild-type (WT) mitochondria. Deletion-bearing worms were rapidly purged within a few generations when competed against WT mitochondrial DNA (mtDNA) bearing worms in experimental populations. By contrast, the Delta ctb-1 mitotype was able to persist in large populations comprising heteroplasmic individuals only, although the average intracellular frequency of Delta ctb-1 exhibited a slow decline owing to competition among individuals bearing different frequencies of the heteroplasmy. Within experimental lines subjected to severe population bottlenecks (n = 1), the relative intracellular frequency of Delta ctb-1 increased, which is a hallmark of selfish drive. A positive correlation between Delta ctb-1 and WT mtDNA copy-number suggests a mechanism that increases total mtDNA per se, and does not discern the Delta ctb-1 mitotype from the WT mtDNA. This study demonstrates the selfish nature of the Delta ctb-1 mitotype, given its transmission advantage and substantial fitness load for the host, and highlights the importance of population size for the population dynamics of selfish mtDNA. This article is part of the theme issue 'Linking the mitochondrial genotype to phenotype: a complex endeavour'.