RT Journal Article SR Electronic T1 C. elegans harbors pervasive cryptic genetic variation for embryogenesis JF bioRxiv FD Cold Spring Harbor Laboratory SP 008532 DO 10.1101/008532 A1 Annalise B. Paaby A1 Amelia G. White A1 David D. Riccardi A1 Kristin C. Gunsalus A1 Fabio Piano A1 Matthew V. Rockman YR 2014 UL http://biorxiv.org/content/early/2014/08/28/008532.abstract AB Conditionally functional mutations are an important class of natural genetic variation, yet little is known about their prevalence in natural populations or their contribution to disease risk. Here, we describe a vast reserve of cryptic genetic variation, alleles that are normally silent but which affect phenotype when the function of other genes is perturbed, in the gene networks of C. elegans embryogenesis. We find evidence that cryptic-effect loci are ubiquitous and segregate at intermediate frequencies in the wild. The cryptic alleles demonstrate low developmental pleiotropy, in that specific, rather than general, perturbations are required to reveal them. Our findings underscore the importance of genetic background in characterizing gene function and provide a model for the expression of conditionally functional effects that may be fundamental in basic mechanisms of trait evolution and the genetic basis of disease susceptibility.