Variability in gene expression underlies incomplete penetrance

The phenotypic differences between individual organisms can often be ascribed to underlying genetic and environmental variation. However, even genetically identical organisms in homogeneous environments vary, indicating that randomness in developmental processes such as gene expression may also generate diversity. To examine the consequences of gene expression variability in multicellular organisms, we studied intestinal specification in the nematode Caenorhabditis elegans in which wild-type cell fate is invariant and controlled by a small transcriptional network. Mutations in elements of this network can have indeterminate effects: some mutant embryos fail to develop intestinal cells, whereas others produce intestinal precursors. By counting transcripts of the genes in this network in individual embryos, we show that the expression of an otherwise redundant gene becomes highly variable in the mutants and that this variation is subjected to a threshold, producing an ON/OFF expression pattern of the master regulatory gene of intestinal differentiation. Our results demonstrate that mutations in developmental networks can expose otherwise buffered stochastic variability in gene expression, leading to pronounced phenotypic variation.National Institutes of Health (U.S.). Pioneer AwardMathematical Sciences Postdoctoral Research Fellowships (DMS-0603392)National Institutes of Health (U.S.). Ruth L. Kirschstein National Research Service Award (5F32GM080966

Phenotypic plasticity: From microevolution to macroevolution

International audienceThis chapter starts with a short history of the concept of phenotypic plasticity (from the seventeenth century to present) in order to distinguish two distinct conceptions of plasticity: one more dynamic (or Aristotelian) according to which the notion has been described as a property inherent to life whose very organization depends upon it, and an other conception, more passive, according to which " plasticity " means the capacity to express different phenotypes for a single genotype depending on environmental conditions. The chapter shows then how Darwinian theories have first favored the second conception, before the emergence of a renewed interest for the first one, which plays the role of an explanans, while the second conception would rather be an explanandum. In so doing, the chapter describes in depth the role of the concept in micro-and macroevolution study. The concept of plasticity is everywhere in the life sciences. As in philosophy, 1 the term can have two meanings: in the active sense, the concept of plasticity is synonymous with " that which has the power to shape or form " with the example in biology being the egg cell development, which has the plastic capacity to generate a mul-ti-celled organism; in the passive sense, the concept expresses a " susceptibility to take on an indefinite number of forms " , with the example in evolutionary biology being " phenotypic plasticity " , which we will define here as an organisms' capacity to express different phenotypes of a single genotype as a function of environmental conditions. The concept of plasticity is then, in its passive sense, linked to evolu-1 Godin (2004), Dictionnaire de philosophie, Fayard/éditions du Temps