Dissecting cryptic variation
Organisms tend to be robust and invariant, harboring 'cryptic' genetic variation that has no apparent effect on phenotypes. The nature of this variation, and the evolution of robustness, has only begun to be explored. Josselin Milloz and colleagues now report a quantitative assessment of variation in a developmental signaling network that underlies vulva cell fate patterning in Caenorhabditis elegans (Genes Dev. 22, 3064–3075; 2008). The vulva develops from a stereotypical pattern of cell-fate decisions, and is known to be regulated by an EGF receptor–dependent pathway through Ras and MAPK, as well as Notch and Wnt signals. The authors analyzed seven independent wild isolates of C. elegans, introgressing mutations in the Ras, Notch and Wnt pathways, and scoring the number of induced vulval cells. They found that variation in Ras signaling has markedly different effects on the phenotype, suggesting the presence of cryptic variation in this pathway. Transgenic reporter constructs that quantitatively measure Ras output reveal that lines with higher background levels of Ras signaling have a higher vulval-cell inductive index in the Ras-mutation introgression assay. The effect of the Ras pathway mutations was largely uncorrelated across tissues, suggesting that robustness in this context has a degree of tissue-specificity. AP
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