Table_5_Identification of Specific Nuclear Genetic Loci and Genes That Interact With the Mitochondrial Genome and Contribute to Fecundity in Caenorhabditis elegans.XLSX

Previous studies have found that fecundity is a multigenic trait regulated, in part, by mitochondrial-nuclear (mit-n) genetic interactions. However, the identification of specific nuclear genetic loci or genes interacting with the mitochondrial genome and contributing to the quantitative trait fecundity is an unsolved issue. Here, a panel of recombinant inbred advanced intercrossed lines (RIAILs), established from a cross between the N2 and CB4856 strains of C. elegans, were used to characterize the underlying genetic basis of mit-n genetic interactions related to fecundity. Sixty-seven single nucleotide polymorphisms (SNPs) were identified by association mapping to be linked with fecundity among 115 SNPs linked to mitotype. This indicated significant epistatic effects between nuclear and mitochondria genetics on fecundity. In addition, two specific nuclear genetic loci interacting with the mitochondrial genome and contributing to fecundity were identified. A significant reduction in fecundity was observed in the RIAILs that carried CB4856 mitochondria and a N2 genotype at locus 1 or a CB4856 genotype at locus 2 relative to the wild-type strains. Then, a hybrid strain (CNC10) was established, which was bred as homoplasmic for the CB4856 mtDNA genome and N2 genotype at locus 1 in the CB4856 nuclear background. The mean fecundity of CNC10 was half the fecundity of the control strain. Several functional characteristics of the mitochondria in CNC10 were also influenced by mit-n interactions. Overall, experimental evidence was presented that specific nuclear genetic loci or genes have interactions with the mitochondrial genome and are associated with fecundity. In total, 18 genes were identified using integrative approaches to have interactions with the mitochondrial genome and to contribute to fecundity.

既往研究表明，繁殖力（fecundity）属于多基因性状，其调控部分依赖于线粒体-核（mitochondrial-nuclear, mit-n）遗传互作。但目前仍未解决的科学问题是，如何鉴定与线粒体基因组互作、并对繁殖力这一数量性状产生贡献的特异性核遗传位点或基因。本研究以秀丽隐杆线虫（Caenorhabditis elegans）N2与CB4856菌株杂交构建的重组自交高级互交群体（recombinant inbred advanced intercrossed lines, RIAILs）为实验材料，解析与繁殖力相关的线粒体-核遗传互作的潜在遗传基础。在与线粒体型（mitotype）相关的115个单核苷酸多态性（single nucleotide polymorphisms, SNPs）中，通过关联定位分析鉴定出67个与繁殖力显著关联的SNPs，这表明核遗传与线粒体遗传之间对繁殖力存在显著的上位效应。此外，本研究还鉴定出两个可与线粒体基因组互作并调控繁殖力的特异性核遗传位点。相较于野生型菌株，携带CB4856线粒体且在位点1携带N2基因型，或在位点2携带CB4856基因型的RIAILs，其繁殖力均出现显著下降。随后，我们构建了杂交菌株CNC10，该菌株在CB4856核遗传背景下，其线粒体DNA（mitochondrial DNA, mtDNA）基因组为CB4856型，且位点1携带N2纯合基因型，且线粒体为同质性（homoplasmic）。CNC10的平均繁殖力仅为对照菌株的一半。此外，CNC10中线粒体的多项功能特性也受到线粒体-核遗传互作的影响。综上，本研究提供了实验证据，证明特异性核遗传位点或基因可与线粒体基因组互作并与繁殖力显著相关。通过整合分析方法，本研究共鉴定出18个与线粒体基因组互作并调控繁殖力的基因。