Vertical selection for nuclear and mitochondrial genomes shapes gut microbiota and modifies risks for complex diseases
Vertical selection for nuclear and mitochondrial genomes shapes gut microbiota and modifies risks for complex diseases
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DOI：
10.1152/physiolgenomics.00089.2019
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发表时间：
2020-01-01
影响因子：
4.6
通讯作者：
Joe, Bina
中科院分区：
文献类型：
--
作者：
Zhang, Youjie;Kumarasamy, Sivarajan;Joe, Bina
在这里，我们假设以前仅仅归因于核和线粒体基因组遗传的复杂疾病性状的遗传能力被扩大到包括全基因组的第三个组成部分，微生物组。为了验证这一点，我们将选择性培育的低能力跑者/高能力跑者（LCR/HCR）大鼠运动模型系统扩展为四种不同的大鼠全息模型框架，包括匹配和不匹配的宿主核和线粒体基因组。不同核基因组和线粒体基因组的垂直选择导致这些全息生物模型中微生物组的不同获取。对这些新型模型的多基因疾病风险进行了评估，并随后在受控的实验室环境中将其与微生物组的获取模式和贡献相关联。核-线粒体-微生物的相互作用并不能作为健康的报告，但可以显著增加肥胖、血压升高、心功能受损和长期记忆丧失，作为疾病易感性的报告。这些发现为微生物组与核和线粒体基因组的共选择作为影响复杂疾病遗传力的重要特征提供了证据。
Here we postulate that the heritability of complex disease traits previously ascribed solely to the inheritance of the nuclear and mitochondrial genomes is broadened to encompass a third component of the holobiome, the microbiome. To test this, we expanded on the selectively bred low capacity runner/high capacity runner (LCR/HCR) rat exercise model system into four distinct rat holobiont model frameworks including matched and mismatched host nuclear and mitochondrial genomes. Vertical selection of varying nuclear and mitochondrial genomes resulted in differential acquisition of the microbiome within each of these holobiont models. Polygenic disease risk of these novel models were assessed and subsequently correlated with patterns of acquisition and contributions of their microbiomes in controlled laboratory settings. Nuclear-mitochondrial-microbiotal interactions were not for exercise as a reporter of health, but significantly noted for increased adiposity, increased blood pressure, compromised cardiac function, and loss of long-term memory as reporters of disease susceptibility. These findings provide evidence for coselection of the microbiome with nuclear and mitochondrial genomes as an important feature impacting the heritability of complex diseases.