title: Wild worm embryogenesis harbors ubiquitous polygenic modifier variation.
abstract: Embryogenesis is an essential and stereotypic process that nevertheless evolves among species. Its essentiality may favor the accumulation of cryptic genetic variation (CGV) that has no effect in the wild-type but that enhances or suppresses the effects of rare disruptions to gene function. Here, we adapted a classical modifier screen to interrogate the alleles segregating in natural populations of Caenorhabditis elegans: we induced gene knockdowns and used quantitative genetic methodology to examine how segregating variants modify the penetrance of embryonic lethality. Each perturbation revealed CGV, indicating that wild-type genomes harbor myriad genetic modifiers that may have little effect individually but which in aggregate can dramatically influence penetrance. Phenotypes were mediated by many modifiers, indicating high polygenicity, but the alleles tend to act very specifically, indicating low pleiotropy. Our findings demonstrate the extent of conditional functionality in complex trait architecture.
authors: Department of Biology and Center for Genomics and Systems Biology, New York University, New York, United States.
authors: Annalise B
authors: AB
authors: Paaby
authors: Department of Biology and Center for Genomics and Systems Biology, New York University, New York, United States.
authors: Amelia G
authors: AG
authors: White
authors: Department of Biology and Center for Genomics and Systems Biology, New York University, New York, United States.
authors: David D
authors: DD
authors: Riccardi
authors: Department of Biology and Center for Genomics and Systems Biology, New York University, New York, United States.
authors: Kristin C
authors: KC
authors: Gunsalus
authors: Department of Biology and Center for Genomics and Systems Biology, New York University, New York, United States.
authors: Fabio
authors: F
authors: Piano
authors: Department of Biology and Center for Genomics and Systems Biology, New York University, New York, United States.
authors: Matthew V
authors: MV
authors: Rockman
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000196:embryology* / Q000235:genetics*; D047108:Embryonic Development; D014644:Genetic Variation; D020412:Multifactorial Inheritance; D010641:Phenotype
keywords: C. elegans; cryptic genetic variation; evolutionary biology; genetic background; genomics; modifier variation