Kenney M Cristina, Chwa Marilyn, Atilano Shari R, Falatoonzadeh Payam, Ramirez Claudio, Malik Deepika, Tarek Mohamed, Del Carpio Javier Cáceres, Nesburn Anthony B, Boyer David S, Kuppermann Baruch D, Vawter Marquis P, Jazwinski S Michal, Miceli Michael V, Wallace Douglas C, Udar Nitin
Gavin Herbert Eye Institute, Univ. of California Irvine, Irvine, CA, USA; Department of Pathology and Laboratory Medicine, Univ. of California Irvine, Irvine, CA, USA.
Gavin Herbert Eye Institute, Univ. of California Irvine, Irvine, CA, USA.
Biochim Biophys Acta. 2014 Feb;1842(2):208-19. doi: 10.1016/j.bbadis.2013.10.016. Epub 2013 Nov 4.
The geographic origins of populations can be identified by their maternally inherited mitochondrial DNA (mtDNA) haplogroups. This study compared human cybrids (cytoplasmic hybrids), which are cell lines with identical nuclei but mitochondria from different individuals with mtDNA from either the H haplogroup or L haplogroup backgrounds. The most common European haplogroup is H while individuals of maternal African origin are of the L haplogroup. Despite lower mtDNA copy numbers, L cybrids had higher expression levels for nine mtDNA-encoded respiratory complex genes, decreased ATP (adenosine triphosphate) turnover rates and lower levels of reactive oxygen species production, parameters which are consistent with more efficient oxidative phosphorylation. Surprisingly, GeneChip arrays showed that the L and H cybrids had major differences in expression of genes of the canonical complement system (5 genes), dermatan/chondroitin sulfate biosynthesis (5 genes) and CCR3 (chemokine, CC motif, receptor 3) signaling (9 genes). Quantitative nuclear gene expression studies confirmed that L cybrids had (a) lower expression levels of complement pathway and innate immunity genes and (b) increased levels of inflammation-related signaling genes, which are critical in human diseases. Our data support the hypothesis that mtDNA haplogroups representing populations from different geographic origins may play a role in differential susceptibilities to diseases.
人群的地理起源可以通过其母系遗传的线粒体DNA（mtDNA）单倍群来确定。本研究比较了人类胞质杂种（细胞质杂种），即具有相同细胞核但线粒体来自不同个体的细胞系，这些个体的线粒体DNA具有H单倍群或L单倍群背景。欧洲最常见的单倍群是H，而非洲母系起源的个体属于L单倍群。尽管L胞质杂种的mtDNA拷贝数较低，但9个mtDNA编码的呼吸复合体基因的表达水平较高，三磷酸腺苷（ATP）周转率降低，活性氧产生水平较低，这些参数与更有效的氧化磷酸化一致。令人惊讶的是，基因芯片阵列显示，L和H胞质杂种在经典补体系统基因（5个基因）、硫酸皮肤素/硫酸软骨素生物合成基因（5个基因）和CCR3（趋化因子，CC基序，受体3）信号通路基因（9个基因）的表达上存在重大差异。定量核基因表达研究证实，L胞质杂种（a）补体途径和先天免疫基因的表达水平较低，（b）炎症相关信号基因的水平升高，这些基因在人类疾病中至关重要。我们的数据支持这样一种假设，即代表不同地理起源人群的mtDNA单倍群可能在疾病易感性差异中起作用。
