title: A Caenorhabditis elegans wild type defies the temperature-size rule owing to a single nucleotide polymorphism in tra-3.
abstract: Ectotherms rely for their body heat on surrounding temperatures. A key question in biology is why most ectotherms mature at a larger size at lower temperatures, a phenomenon known as the temperature-size rule. Since temperature affects virtually all processes in a living organism, current theories to explain this phenomenon are diverse and complex and assert often from opposing assumptions. Although widely studied, the molecular genetic control of the temperature-size rule is unknown. We found that the Caenorhabditis elegans wild-type N2 complied with the temperature-size rule, whereas wild-type CB4856 defied it. Using a candidate gene approach based on an N2 x CB4856 recombinant inbred panel in combination with mutant analysis, complementation, and transgenic studies, we show that a single nucleotide polymorphism in tra-3 leads to mutation F96L in the encoded calpain-like protease. This mutation attenuates the ability of CB4856 to grow larger at low temperature. Homology modelling predicts that F96L reduces TRA-3 activity by destabilizing the DII-A domain. The data show that size adaptation of ectotherms to temperature changes may be less complex than previously thought because a subtle wild-type polymorphism modulates the temperature responsiveness of body size. These findings provide a novel step toward the molecular understanding of the temperature-size rule, which has puzzled biologists for decades.
authors.affiliation: Laboratory of Nematology, Wageningen University, Wageningen, The Netherlands. Jan.Kammenga@wur.nl
authors.forename: Jan E
authors.initials: JE
authors.lastname: Kammenga
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Doroszuk
authors.forename: Joost A G
authors.initials: JA
authors.lastname: Riksen
authors.forename: Esther
authors.initials: E
authors.lastname: Hazendonk
authors.forename: Laurentiu
authors.initials: L
authors.lastname: Spiridon
authors.forename: Andrei-Jose
authors.initials: AJ
authors.lastname: Petrescu
authors.forename: Marcel
authors.initials: M
authors.lastname: Tijsterman
authors.forename: Ronald H A
authors.initials: RH
authors.lastname: Plasterk
authors.forename: Jaap
authors.initials: J
authors.lastname: Bakker
mesh_terms: D000483:Alleles; D000818:Animals; D049628:Body Size / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D001831:Body Temperature / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D017173:Caenorhabditis elegans / Q000187:drug effects / Q000235:genetics* / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002154:Calpain; D005786:Gene Expression Regulation / Q000187:drug effects; D017238:Genes, Helminth; D005816:Genetic Complementation Test; D007178:Inbreeding; D008954:Models, Biological; D008958:Models, Molecular; D050505:Mutant Proteins / Q000737:chemistry; D009154:Mutation / Q000235:genetics; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D017434:Protein Structure, Tertiary; D040641:Quantitative Trait Loci; D017422:Sequence Analysis, DNA; D040681:Structural Homology, Protein; D019284:Thapsigargin / Q000494:pharmacology
chemical_list: D029742:Caenorhabditis elegans Proteins; D050505:Mutant Proteins; D019284:Thapsigargin; D002154:Calpain; C102444:TRA-3 protein, C elegans; D002118:Calcium