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首页> 外文期刊>Biochimica et biophysica acta. Molecular basis of disease: BBA >Molecular and bioenergetic differences between cells with African versus European inherited mitochondrial DNA haplogroups: Implications for population susceptibility to diseases
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Molecular and bioenergetic differences between cells with African versus European inherited mitochondrial DNA haplogroups: Implications for population susceptibility to diseases

机译：非洲和欧洲遗传的线粒体DNA单倍型细胞之间的分子和生物能差异：对人群易感性的影响

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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.
机译：人口的地理起源可以通过其母系遗传的线粒体DNA（mtDNA）单倍型来识别。这项研究比较了人类混合细胞（细胞质杂种），它们是具有相同核但来自不同个体的线粒体的细胞系，具有来自H单倍群或L单倍群背景的mtDNA。欧洲最常见的单倍群是H，而源自非洲的母性个体是L单倍群。尽管mtDNA拷贝数较低，但L cybrids对9个mtDNA编码的呼吸道复合基因具有较高的表达水平，降低了ATP（三磷酸腺苷）周转率，降低了活性氧的产生水平，这些参数与更有效的氧化磷酸化相一致。令人惊讶的是，GeneChip阵列显示L和H杂种在经典补体系统基因（5个基因），硫酸皮肤素/软骨素生物合成（5个基因）和CCR3（趋化因子，CC基序，受体3）信号的表达上有主要差异（ 9个基因）。定量核基因表达研究证实，L cybrids具有（a）较低的补体途径和先天免疫基因表达水平，以及（b）与炎症相关的信号基因水平升高，这对人类疾病至关重要。我们的数据支持以下假设：代表来自不同地理起源人群的mtDNA单倍型可能在对疾病的易感性中起作用。

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