Exceptional evolutionary divergence of human muscle and brain metabolomes parallels human cognitive and physical uniqueness.
Exceptional evolutionary divergence of human muscle and brain metabolomes parallels human cognitive and physical uniqueness.
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人类肌肉和大脑代谢组的异常进化差异与人类认知和身体独特性相似
DOI：
10.1371/journal.pbio.1001871
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发表时间：
2014-05
期刊：
影响因子：
9.8
通讯作者：
Khaitovich P
中科院分区：
文献类型：
--
作者：
Bozek K;Wei Y;Yan Z;Liu X;Xiong J;Sugimoto M;Tomita M;Pääbo S;Pieszek R;Sherwood CC;Hof PR;Ely JJ;Steinhauser D;Willmitzer L;Bangsbo J;Hansson O;Call J;Giavalisco P;Khaitovich P
人类大脑和肌肉代谢组的加速进化反映了我们独特的认知和身体能力。代谢物浓度反映了组织和细胞的生理状态。然而，代谢变化在物种进化中的作用目前尚不清楚。在这里，我们提出了一项基于超过10，000种亲水化合物在人类，黑猩猩，猕猴和小鼠的三个大脑区域和两个非神经组织中进行的代谢组进化研究。虽然黑猩猩，猕猴和小鼠的代谢组分歧物种之间的遗传距离，我们检测到显着加速人类前额叶皮层和骨骼肌影响神经和能量代谢途径的代谢组进化。这些代谢变化不能归因于环境条件，并根据其相应酶的表达进行了确认。我们进一步对人类、黑猩猩和猕猴进行了肌肉力量测试。结果表明，虽然人类具有上级认知能力，但他们的肌肉表现可能明显不如黑猩猩和猕猴。维持我们组织功能的生理过程涉及多种产物和中间体的产生，称为代谢物-重量小于1，500道尔顿的小分子。这些代谢物的浓度变化被认为与表型变化密切相关。在这里，我们使用基于质谱的方法评估了人类，黑猩猩，猕猴和小鼠的三个大脑区域和两个非神经组织（骨骼肌和肾脏）中超过10，000种代谢物的浓度。我们发现，代谢组的进化在很大程度上反映了物种之间的遗传差异，并没有很大的环境因素的影响。然而，在人类谱系中，我们观察到大脑前额叶皮层区域和骨骼肌中代谢组进化的异常加速。基于额外的行为测试，我们进一步表明，人体肌肉的代谢变化似乎被肌肉力量的急剧下降所掩盖。观察到的大脑和肌肉的快速代谢变化，以及独特的人类认知技能和低肌肉性能，可能反映了人类进化中的平行机制。
Accelerated evolution of the human brain and muscle metabolomes reflects our unique cognitive and physical capacities. Metabolite concentrations reflect the physiological states of tissues and cells. However, the role of metabolic changes in species evolution is currently unknown. Here, we present a study of metabolome evolution conducted in three brain regions and two non-neural tissues from humans, chimpanzees, macaque monkeys, and mice based on over 10,000 hydrophilic compounds. While chimpanzee, macaque, and mouse metabolomes diverge following the genetic distances among species, we detect remarkable acceleration of metabolome evolution in human prefrontal cortex and skeletal muscle affecting neural and energy metabolism pathways. These metabolic changes could not be attributed to environmental conditions and were confirmed against the expression of their corresponding enzymes. We further conducted muscle strength tests in humans, chimpanzees, and macaques. The results suggest that, while humans are characterized by superior cognition, their muscular performance might be markedly inferior to that of chimpanzees and macaque monkeys. Physiological processes that maintain our tissues' functionality involve the generation of multiple products and intermediates known as metabolites—small molecules with a weight of less than 1,500 Daltons. Changes in concentrations of these metabolites are thought to be closely related to changes in phenotype. Here, we assessed concentrations of more than 10,000 metabolites in three brain regions and two non-neural tissues (skeletal muscle and kidney) of humans, chimpanzees, macaque monkeys, and mice using mass spectrometry-based approaches. We found that the evolution of the metabolome largely reflects genetic divergence between species and is not greatly affected by environmental factors. In the human lineage, however, we observed an exceptional acceleration of metabolome evolution in the prefrontal cortical region of the brain and in skeletal muscle. Based on additional behavioral tests, we further show that metabolic changes in human muscle seem to be paralleled by a drastic reduction in muscle strength. The observed rapid metabolic changes in brain and muscle, together with the unique human cognitive skills and low muscle performance, might reflect parallel mechanisms in human evolution.
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影响因子：
48
作者：
Langmead, Ben;Salzberg, Steven L.
通讯作者：
Salzberg, Steven L.
影响因子：
14.9
作者：
Kanehisa M;Goto S;Sato Y;Furumichi M;Tanabe M
通讯作者：
Tanabe M
DOI：
10.2307/1373587
发表时间：
1926-01-01
期刊：
JOUR MAMMALOGY
影响因子：
--
作者：
BAUMAN, JOHN E.
通讯作者：
BAUMAN, JOHN E.
DOI：
10.1111/j.1749-6632.1977.tb38182.x
发表时间：
1977-01-01
影响因子：
5.2
作者：
Saltin, B;Henriksson, J;Jansson, E
通讯作者：
Jansson, E
影响因子：
1.7
作者：
Carlson, Kristian J.
通讯作者：
Carlson, Kristian J.