小柯机器人

美国马萨诸塞大学Albertha J. M. Walhout、康奈尔大学Frank C. Schroeder和西北大学Erik C. Andersen团队合作表明，秀丽隐杆线虫可作为个体间代谢差异模型。2022年7月6日出版的《自然》杂志发表了这项成果。

研究人员以秀丽隐杆线虫作为模型研究了个体间的代谢差异。通过比较三种野生菌株和常用的N2实验室菌株，研究发现已知代谢物的丰度与之前研究没有揭示过的代谢物丰度间存在差异。后一种代谢物包括3-羟基丙酸(3HP)和几种氨基酸(3HP-AAs)之间的结合物，其中一种在野生菌株的丰度要高得多。3HP是丙酸分流途径中的一种中间体，当经典的、维生素B12依赖性丙酸分解途径通量受到干扰时，该途径被激活。研究发现3HP-AAs积累增加是由HPHD-1遗传变异引起的，其中3HP是底物。

该研究结果表明，3HP-AAs的产生代表了一种“分流内分流”途径，以适应hphd-1等位基因减少。这项研究为研发代谢网络模型提供了依据，该模型捕捉了个体特定的代谢差异，更可以代表整个物种的多样性。

研究人员表示，由于遗传背景、营养摄入、微生物群和其他环境因素的相互作用，个体可能表现出新陈代谢差异。由于饮食和生活方式等方面的差异，很难将新陈代谢的差异与基因组变异联系起来，并得出潜在的分子机制。

附：英文原文

Title: C. elegans as a model for inter-individual variation in metabolism

Author: Fox, Bennett W., Ponomarova, Olga, Lee, Yong-Uk, Zhang, Gaotian, Giese, Gabrielle E., Walker, Melissa, Roberto, Nicole M., Na, Huimin, Rodrigues, Pedro R., Curtis, Brian J., Kolodziej, Aiden R., Crombie, Timothy A., Zdraljevic, Stefan, Yilmaz, L. Safak, Andersen, Erik C., Schroeder, Frank C., Walhout, Albertha J. M.

Issue&Volume: 2022-07-06

Abstract: Individuals can exhibit differences in metabolism that are caused by the interplay of genetic background, nutritional input, microbiota and other environmental factors1,2,3,4. It is difficult to connect differences in metabolism to genomic variation and derive underlying molecular mechanisms in humans, owing to differences in diet and lifestyle, among others. Here we use the nematode Caenorhabditis elegans as a model to study inter-individual variation in metabolism. By comparing three wild strains and the commonly used N2 laboratory strain, we find differences in the abundances of both known metabolites and those that have not to our knowledge been previously described. The latter metabolites include conjugates between 3-hydroxypropionate (3HP) and several amino acids (3HP-AAs), which are much higher in abundance in one of the wild strains. 3HP is an intermediate in the propionate shunt pathway, which is activated when flux through the canonical, vitamin-B12-dependent propionate breakdown pathway is perturbed5. We show that increased accumulation of 3HP-AAs is caused by genetic variation in HPHD-1, for which 3HP is a substrate. Our results suggest that the production of 3HP-AAs represents a ‘shunt-within-a-shunt’ pathway to accommodate a reduction-of-function allele in hphd-1. This study provides a step towards the development of metabolic network models that capture individual-specific differences of metabolism and more closely represent the diversity that is found in entire species.

DOI: 10.1038/s41586-022-04951-3

Source: https://www.nature.com/articles/s41586-022-04951-3

Nature：《自然》，创刊于1869年。隶属于施普林格·自然出版集团，最新IF：69.504
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