Caenorhabditis elegans Genes Affecting Interindividual Variation in Life-span Biomarker Gene Expression.
Genetically identical organisms grown in homogenous environments differ in quantitative phenotypes. Differences in one such trait, expression of a single biomarker gene, can identify isogenic cells or organisms that later manifest different fates. For example, in isogenic populations of young adult Caenorhabditis elegans, differences in Green Fluorescent Protein (GFP) expressed from the hsp-16.2 promoter predict differences in life span. Thus, it is of interest to determine how interindividual differences in biomarker gene expression arise. Prior reports showed that the thermosensory neurons and insulin signaling systems controlled the magnitude of the heat shock response, including absolute expression of hsp-16.2. Here, we tested whether these regulatory signals might also influence variation in hsp-16.2 reporter expression. Genetic experiments showed that the action of AFD thermosensory neurons increases interindividual variation in biomarker expression. Further genetic experimentation showed the insulin signaling system acts to decrease interindividual variation in life-span biomarker expression; in other words, insulin signaling canalizes expression of the hsp-16.2-driven life-span biomarker. Our results show that specific signaling systems regulate not only expression level, but also the amount of interindividual expression variation for a life-span biomarker gene. They raise the possibility that manipulation of these systems might offer means to reduce heterogeneity in the aging process.
Department of Pathology, University of Washington, Seattle.
Alexander
A
Mendenhall
Department of Pathology, University of Washington, Seattle.
Matthew M
MM
Crane
Institute for Behavioral Genetics.
Patricia M
PM
Tedesco
Institute for Behavioral Genetics.|Department of Integrative Physiology.|Biofrontiers Institute, University of Colorado, Boulder.
Thomas E
TE
Johnson
Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington.
Roger
R
Brent
D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics; D015870:Gene Expression; D017238:Genes, Helminth; D017930:Genes, Reporter / Q000235:genetics*; D005819:Genetic Markers; D014644:Genetic Variation; D049452:Green Fluorescent Proteins / Q000235:genetics; D006360:Heat-Shock Proteins / Q000235:genetics*; D018869:Heat-Shock Response; D008136:Longevity / Q000235:genetics*; D010641:Phenotype; D015398:Signal Transduction
D029742:Caenorhabditis elegans Proteins; D005819:Genetic Markers; D006360:Heat-Shock Proteins; D049452:Green Fluorescent Proteins
Aging; Heat shock; Nongenetic