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Metabotyping of Caenorhabditis elegans reveals latent phenotypes.

ABSTRACT: Assigning functions to every gene in a living organism is the next challenge for functional genomics. In fact, 85-90% of the 19,000 genes of the nematode Caenorhabditis elegans genome do not produce any visible phenotype when inactivated, which hampers determining their function, especially when they do not belong to previously characterized gene families. We used (1)H high-resolution magic angle spinning NMR spectroscopy ((1)H HRMAS-NMR) to reveal the latent phenotype associated to superoxide dismutase (sod-1) and catalase (ctl-1) C. elegans mutations, both involved in the elimination of radical oxidative species. These two silent mutations are significantly discriminated from the wild-type strain and from each other. We identify a metabotype significantly associated with these mutations involving a general reduction of fatty acyl resonances from triglycerides, unsaturated lipids being known targets of free radicals. This work opens up perspectives for the use of (1)H HRMAS-NMR as a molecular phenotyping device for model organisms. Because it is amenable to high throughput and is shown to be highly informative, this approach may rapidly lead to a functional and integrated metabonomic mapping of the C. elegans genome at the systems biology level.

SUBMITTER: Blaise BJ

PROVIDER: S-EPMC2148380 | biostudies-literature | 2007 Dec

REPOSITORIES: biostudies-literature

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Metabotyping of Caenorhabditis elegans reveals latent phenotypes.

Blaise Benjamin J BJ Giacomotto Jean J Elena Bénédicte B Dumas Marc-Emmanuel ME Toulhoat Pierre P Ségalat Laurent L Emsley Lyndon L

Proceedings of the National Academy of Sciences of the United States of America 20071205 50

Assigning functions to every gene in a living organism is the next challenge for functional genomics. In fact, 85-90% of the 19,000 genes of the nematode Caenorhabditis elegans genome do not produce any visible phenotype when inactivated, which hampers determining their function, especially when they do not belong to previously characterized gene families. We used (1)H high-resolution magic angle spinning NMR spectroscopy ((1)H HRMAS-NMR) to reveal the latent phenotype associated to superoxide d ...[more]

PMID: 18077412

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Project description:One of the biggest challenges in biology is to understand how activity at the cellular level of neurons, as a result of their mutual interactions, leads to the observed behavior of an organism responding to a variety of environmental stimuli. Investigating the intermediate or mesoscopic level of organization in the nervous system is a vital step towards understanding how the integration of micro-level dynamics results in macro-level functioning. The coordination of many different co-occurring processes at this level underlies the command and control of overall network activity. In this paper, we have considered the somatic nervous system of the nematode Caenorhabditis elegans, for which the entire neuronal connectivity diagram is known. We focus on the organization of the system into modules, i.e., neuronal groups having relatively higher connection density compared to that of the overall network. We show that this mesoscopic feature cannot be explained exclusively in terms of considerations such as, optimizing for resource constraints (viz., total wiring cost) and communication efficiency (i.e., network path length). Even including information about the genetic relatedness of the cells cannot account for the observed modular structure. Comparison with other complex networks designed for efficient transport (of signals or resources) implies that neuronal networks form a distinct class. This suggests that the principal function of the network, viz., processing of sensory information resulting in appropriate motor response, may be playing a vital role in determining the connection topology. Using modular spectral analysis we make explicit the intimate relation between function and structure in the nervous system. This is further brought out by identifying functionally critical neurons purely on the basis of patterns of intra- and inter-modular connections. Our study reveals how the design of the nervous system reflects several constraints, including its key functional role as a processor of information.

Dataset Information

Metabotyping of Caenorhabditis elegans reveals latent phenotypes.

Publications

Metabotyping of Caenorhabditis elegans reveals latent phenotypes.

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