Oxidative phosphorylation is among the most conserved mitochondrial pathways. However, one of the cornerstones of this pathway, the multi-protein complex NADH : ubiquinone oxidoreductase (complex I) has been lost multiple independent times in diverse eukaryotic lineages. The causes and consequences of these convergent losses remain poorly understood. Here, we used a comparative genomics approach to reconstruct evolutionary paths leading to complex I loss and infer possible evolutionary scenarios. By mining available mitochondrial and nuclear genomes, we identified eight independent events of mitochondrial complex I loss across eukaryotes, of which six occurred in fungal lineages. We focused on three recent loss events that affect closely related fungal species, and inferred genomic changes convergently associated with complex I loss. Based on these results, we predict novel complex I functional partners and relate the loss of complex I with the presence of increased mitochondrial antioxidants, higher fermentative capabilities, duplications of alternative dehydrogenases, loss of alternative oxidases and adaptation to antifungal compounds. To explain these findings, we hypothesize that a combination of previously acquired compensatory mechanisms and exposure to environmental triggers of oxidative stress (such as hypoxia and/or toxic chemicals) induced complex I loss in fungi.

氧化磷酸化是最保守的线粒体途径之一。然而，作为该途径的基石之一，多蛋白复合物 NADH：泛醌氧化还原酶（复合物 I）在不同的真核生物谱系中已独立多次丢失。这些趋同损失的原因和后果仍然知之甚少。在这里，我们使用比较基因组学方法来重建导致复杂 I 损失的进化路径并推断可能的进化场景。通过挖掘可用的线粒体和核基因组，我们确定了真核生物中线粒体复合物 I 丢失的 8 个独立事件，其中 6 个发生在真菌谱系中。我们专注于影响密切相关的真菌物种的三个最近的损失事件，并推断基因组变化与复杂的 I 损失密切相关。基于这些结果，我们预测了新的复合物 I 功能伙伴，并将复合物 I 的损失与线粒体抗氧化剂的增加、更高的发酵能力、替代脱氢酶的复制、替代氧化酶的损失和对抗真菌化合物的适应联系起来。为了解释这些发现，我们假设先前获得的补偿机制和暴露于氧化应激的环境触发因素（如缺氧和/或有毒化学物质）的组合会导致真菌中复合物 I 的损失。