Long-Range Regulatory Polymorphisms Affecting a GABA Receptor Constitute a Quantitative Trait Locus (QTL) for Social Behavior in Caenorhabditis elegans

Andres Bendesky, Jason Pitts, Matthew Rockman, William C. Chen, Man Wah Tan, Leonid Kruglyak, Cornelia I. Bargmann

Research output: Contribution to journalArticle

Abstract

Aggregation is a social behavior that varies between and within species, providing a model to study the genetic basis of behavioral diversity. In the nematode Caenorhabditis elegans, aggregation is regulated by environmental context and by two neuromodulatory pathways, one dependent on the neuropeptide receptor NPR-1 and one dependent on the TGF-β family protein DAF-7. To gain further insight into the genetic regulation of aggregation, we characterize natural variation underlying behavioral differences between two wild-type C. elegans strains, N2 and CB4856. Using quantitative genetic techniques, including a survey of chromosome substitution strains and QTL analysis of recombinant inbred lines, we identify three new QTLs affecting aggregation in addition to the two known N2 mutations in npr-1 and glb-5. Fine-mapping with near-isogenic lines localized one QTL, accounting for 5%-8% of the behavioral variance between N2 and CB4856, 3′ to the transcript of the GABA neurotransmitter receptor gene exp-1. Quantitative complementation tests demonstrated that this QTL affects exp-1, identifying exp-1 and GABA signaling as new regulators of aggregation. exp-1 interacts genetically with the daf-7 TGF-β pathway, which integrates food availability and population density, and exp-1 mutations affect the level of daf-7 expression. Our results add to growing evidence that genetic variation affecting neurotransmitter receptor genes is a source of natural behavioral variation.

Original languageEnglish (US)
Article numbere1003157
JournalPLoS Genetics
Volume8
Issue number12
DOIs
StatePublished - Dec 2012

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GABA Receptors
Social Behavior
Quantitative Trait Loci
social behavior
Caenorhabditis elegans
quantitative trait loci
polymorphism
Neurotransmitter Receptor
genetic polymorphism
Genetic Complementation Test
Neuropeptide Receptors
Behavioral Genetics
Genetic Techniques
Mutation
chromosome substitution
Population Density
mutation
gamma-Aminobutyric Acid
Genes
gamma-aminobutyric acid

ASJC Scopus subject areas

  • Genetics
  • Molecular Biology
  • Ecology, Evolution, Behavior and Systematics
  • Cancer Research
  • Genetics(clinical)

Cite this

Long-Range Regulatory Polymorphisms Affecting a GABA Receptor Constitute a Quantitative Trait Locus (QTL) for Social Behavior in Caenorhabditis elegans. / Bendesky, Andres; Pitts, Jason; Rockman, Matthew; Chen, William C.; Tan, Man Wah; Kruglyak, Leonid; Bargmann, Cornelia I.

In: PLoS Genetics, Vol. 8, No. 12, e1003157, 12.2012.

Research output: Contribution to journalArticle

Bendesky, Andres ; Pitts, Jason ; Rockman, Matthew ; Chen, William C. ; Tan, Man Wah ; Kruglyak, Leonid ; Bargmann, Cornelia I. / Long-Range Regulatory Polymorphisms Affecting a GABA Receptor Constitute a Quantitative Trait Locus (QTL) for Social Behavior in Caenorhabditis elegans. In: PLoS Genetics. 2012 ; Vol. 8, No. 12.
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