Department of Ecology and Evolutionary Biology, Box G, Brown University, Providence, RI, 02912, USA.
Present Address: Department of Biology, University of Maryland, College Park, MD, 20742, USA.
BMC Genomics. 2019 Sep 2;20(1):691. doi: 10.1186/s12864-019-6061-y.
Mitochondria perform many key roles in their eukaryotic hosts, from integrating signaling pathways through to modulating whole organism phenotypes. The > 1 billion years of nuclear and mitochondrial gene co-evolution has necessitated coordinated expression of gene products from both genomes that maintain mitochondrial, and more generally, eukaryotic cellular function. How mitochondrial DNA (mtDNA) variation modifies host fitness has proved a challenging question but has profound implications for evolutionary and medical genetics. In Drosophila, we have previously shown that recently diverged mtDNA haplotypes within-species can have more impact on organismal phenotypes than older, deeply diverged haplotypes from different species. Here, we tested the effects of mtDNA haplotype variation on gene expression in Drosophila under standardized conditions. Using the Drosophila Genetic Reference Panel (DGRP), we constructed a panel of mitonuclear genotypes that consists of factorial variation in nuclear and mtDNA genomes, with mtDNAs originating in D. melanogaster (2x haplotypes) and D. simulans (2x haplotypes).
We show that mtDNA haplotype variation unequivocally alters nuclear gene expression in both females and males, and mitonuclear interactions are pervasive modifying factors for gene expression. There was appreciable overlap between the sexes for mtDNA-sensitive genes, and considerable transcriptional variation attributed to particular mtDNA contrasts. These genes are generally found in low-connectivity gene co-expression networks, occur in gene clusters along chromosomes, are often flanked by non-coding RNA, and are under-represented among housekeeping genes. Finally, we identify the giant (gt) transcription factor motif as a putative regulatory sequence associated with mtDNA-sensitive genes.
There are predictive conditions for nuclear genes that are influenced by mtDNA variation.
线粒体在其真核宿主中发挥着许多关键作用，从整合信号通路到调节整个生物体的表型。>10 亿年的核和线粒体基因协同进化，需要协调来自两个基因组的基因产物的表达，以维持线粒体，更普遍地说，维持真核细胞的功能。线粒体 DNA (mtDNA) 变异如何改变宿主适应性是一个具有挑战性的问题，但对进化和医学遗传学具有深远的影响。在果蝇中，我们之前已经表明，物种内最近分化的 mtDNA 单倍型对生物体表型的影响比来自不同物种的更古老、分化更深的单倍型更大。在这里，我们在标准化条件下测试了 mtDNA 单倍型变异对果蝇基因表达的影响。我们使用果蝇遗传参考面板 (DGRP) 构建了一个由核和 mtDNA 基因组的因子变异组成的 mitonuclear 基因型面板，其中 mtDNA 来自 D. melanogaster（2x 单倍型）和 D. simulans（2x 单倍型）。
我们表明，mtDNA 单倍型变异在雌性和雄性中都能明确改变核基因表达，并且 mitonuclear 相互作用是普遍的基因表达修饰因子。在雌雄两性之间，mtDNA 敏感基因有相当大的重叠，并且有相当大的转录变异归因于特定的 mtDNA 对比。这些基因通常存在于低连接性基因共表达网络中，在染色体上的基因簇中发生，通常被非编码 RNA 包围，并且在管家基因中代表性不足。最后，我们确定了巨大 (gt) 转录因子基序是与 mtDNA 敏感基因相关的潜在调节序列。
存在受 mtDNA 变异影响的核基因的预测条件。
