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Linking Genomic and Metabolomic Natural Variation Uncovers Nematode Pheromone Biosynthesis.

Jan M Falcke | Neelanjan Bose | Alexander B Artyukhin | Christian Rödelsperger | Gabriel V Markov | Joshua J Yim | Dominik Grimm | Marc H Claassen | Oishika Panda | Joshua A Baccile | Ying K Zhang | Henry H Le | Dino Jolic | Frank C Schroeder | Ralf J Sommer
Cell chemical biology | 2018

In the nematodes Caenorhabditis elegans and Pristionchus pacificus, a modular library of small molecules control behavior, lifespan, and development. However, little is known about the final steps of their biosynthesis, in which diverse building blocks from primary metabolism are attached to glycosides of the dideoxysugar ascarylose, the ascarosides. We combine metabolomic analysis of natural isolates of P. pacificus with genome-wide association mapping to identify a putative carboxylesterase, Ppa-uar-1, that is required for attachment of a pyrimidine-derived moiety in the biosynthesis of ubas#1, a major dauer pheromone component. Comparative metabolomic analysis of wild-type and Ppa-uar-1 mutants showed that Ppa-uar-1 is required specifically for the biosynthesis of ubas#1 and related metabolites. Heterologous expression of Ppa-UAR-1 in C. elegans yielded a non-endogenous ascaroside, whose structure confirmed that Ppa-uar-1 is involved in modification of a specific position in ascarosides. Our study demonstrates the utility of natural variation-based approaches for uncovering biosynthetic pathways.

Pubmed ID: 29779955

Research resources used in this publication

None found

Antibodies used in this publication

None found

Associated grants

  • Agency: NIGMS NIH HHS, United States
    Id: R01 GM088290
  • Agency: NIGMS NIH HHS, United States
    Id: R01 GM113692
  • Agency: NIGMS NIH HHS, United States
    Id: T32 GM008500
  • Agency: Howard Hughes Medical Institute, United States

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This is a list of tools and resources that we have found mentioned in this publication.


Pristionchus.org (tool)

RRID:SCR_003414

This data resource is a genetic, molecular, and genomic toolkit that establishes one particular species, Pristionchus pacificus, as a major satellite system for evolutionary developmental biology. Users may download Pristionchus Sequences and use the Pristionchus pacificus genome browser where they may find gene or gene prediction data. Users can also use the BLAST feature, which allows users to search the assembly for position information of bacs, reads and contigs using the mapping tool. The center of the site's research is the evolutionary analysis of vulva formation. The general aim of the Department is to develop the nematode vulva as a suitable case study into the evolutionary alterations of developmental processes. By studying and comparing two distantly related species of the same phylum, such as P. pacificus and C. elegans, macroevolutionary alterations of developmental processes and mechanisms can be identified. The final goal of the Department is to achieve a comprehensive description of macro- and microevolutionary changes of developmental mechanisms at the molecular level in a phylogenetic and ecological context.

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New England Biolabs (tool)

RRID:SCR_013517

An Antibody supplier

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Thermo Xcalibur (tool)

RRID:SCR_014593

A software which acquires and processes data sets, primarily through the Xcalibur system.

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PhyML (tool)

RRID:SCR_014629

Web phylogeny server based on the maximum-likelihood principle.

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Microsoft Excel (tool)

RRID:SCR_016137

Software application with data analysis tools and spreadsheet templates to track and visualize data. It is used to manage and process data.

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