Pleiotropy is the fact that a single gene or mutation may affect several traits. It is a key characteristic of the genetic structure that influences evolutionary trajectories. Pleiotropy has been studied from multiple viewpoints, including evolutionary and functional genomics, quantitative genetics, and theoretical modelling; these perspectives are often difficult to reconcile. In molecular evolution, it is generally acknowledged that pleiotropy is common and promotes genetic conservation; mutations in regulatory sequences, whose modularity relieves the pleiotropy constraint, are then presumably the main road to adaptation. In quantitative genetics, genetic crosses demonstrate that the extent of pleiotropy is limited therefore it is not considered as a significant constraint. Recent models and experimental findings even propose that correlated changes between traits can be advantageous and that, in this case, pleiotropic mutations could facilitate adaptation.
Hence the question remains on how do organisms adapt when many mutations have pleiotropic effects, which are likely antagonistic in many situations? For adaptation to proceed with pleiotropic mutations, their antagonistic effects must be purged or compensated by developmental mechanisms, as in a model proposed by Pavlicev and Wagner. Along this line we think that pleiotropy may promote the divergence of developmental gene expression and cis-regulatory sequences, rather than their conservation.
To test this hypothesis empirically, we need to: 1) Link different levels of variation (genetic, development, morphology) in an organ submitted to strong evolutionary pressures, including adaptation. 2) Focus on a manageable case of pleiotropy involving only two organs, because it is impossible to consider antagonist effects for all organs of an organism. 3) Compare rates and modes of evolution in situations with different pleiotropy constraints. In silico, it is possible to perform evolutionary simulations of two organs evolution “with” and “without” pleiotropy. In vivo, we can compare the evolution of two organs in situations where antagonistic pleiotropy is milder or stronger. 4) Anticipate precisely where developmental compensations and compensatory mutations may occur to focus our efforts. We do that by comparing upper and lower molar development in different species of rodents.
