Comparative metabolomics in primates reveals the effects of diet and gene regulatory variation on metabolic divergence
Comparative metabolomics in primates reveals the effects of diet and gene regulatory variation on metabolic divergence
复制标题
DOI：
10.1038/srep05809
复制
发表时间：
2014-07-28
影响因子：
4.6
通讯作者：
Gilad, Yoav
中科院分区：
文献类型：
--
作者：
Blekhman, Ran;Perry, George H.;Gilad, Yoav
人类的饮食与非人类的灵长类不同。在少数几个明显的差异中，人类比大多数非人类灵长类消费更多的肉类，并定期做饭。人们假设，人类进化过程中的饮食变化伴随着代谢途径中的分子适应。与这一概念一致，对灵长类动物基因表达水平的比较研究发现，具有代谢功能的基因的调节往往在人类谱系中进化得很快。然而，这些调控差异的新陈代谢后果仍不清楚。为了解决这一差距，我们在人类、黑猩猩和恒河猴的肝脏中进行了一项结合基因表达和代谢组谱的比较研究。我们表明，物种间的饮食差异对代谢浓度有很大的影响。此外，我们发现，物种间代谢浓度的差异与控制相同代谢反应的相应酶的物种间表达差异相关。我们确定了一些具有谱系特异性的代谢化合物，包括可能与饮食差异直接相关的人类-物种代谢差异的例子。
Human diets differ from those of non-human primates. Among few obvious differences, humans consume more meat than most non-human primates and regularly cook their food. It is hypothesized that a dietary shift during human evolution has been accompanied by molecular adaptations in metabolic pathways. Consistent with this notion, comparative studies of gene expression levels in primates have found that the regulation of genes with metabolic functions tend to evolve rapidly in the human lineage. The metabolic consequences of these regulatory differences, however, remained unknown. To address this gap, we performed a comparative study using a combination of gene expression and metabolomic profiling in livers from humans, chimpanzees, and rhesus macaques. We show that dietary differences between species have a strong effect on metabolic concentrations. In addition, we found that differences in metabolic concentration across species are correlated with inter-species differences in the expression of the corresponding enzymes, which control the same metabolic reaction. We identified a number of metabolic compounds with lineage-specific profiles, including examples of human-species metabolic differences that may be directly related to dietary differences.