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

Autor: Bennett W. Fox, Olga Ponomarova, Yong-Uk Lee, Gaotian Zhang, Gabrielle E. Giese, Melissa Walker, Nicole M. Roberto, Huimin Na, Pedro R. Rodrigues, Brian J. Curtis, Aiden R. Kolodziej, Timothy A. Crombie, Stefan Zdraljevic, L. Safak Yilmaz, Erik C. Andersen, Frank C. Schroeder, Albertha J. M. Walhout
Rok vydání: 2022
Předmět:
Zdroj: Nature
ISSN: 1476-4687
0028-0836
DOI: 10.1038/s41586-022-04951-3
Popis: Individuals can exhibit differences in metabolism caused by the interplay of genetic background, nutritional input, microbiota, and other environmental factors(1–4). It is difficult to connect differences in metabolism to genomic variation and derive underlying molecular mechanisms in humans due to differences in diet and lifestyle, among others. Here, we introduce 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 and previously undescribed metabolites. Novel metabolites include conjugates between 3-hydroxypropionate (3HP) and several amino acids (3HP-AAs) that 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 perturbed(5). We demonstrate that increased 3HP-AA accumulation is caused by genetic variation in HPHD-1, for which 3HP is a substrate. Our results suggest that 3HP-AA production represents a ‘shunt-within-a-shunt’ pathway to accommodate a reduction-of-function allele in hphd-1. This study provides a first step to developing metabolic network models that capture individual-specific differences of metabolism and more closely represent the diversity found in entire species.
Databáze: OpenAIRE
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