pleiotropy & compensatory evolution

Pavlicev M & Wagner GP 2012 A model of developmental evolution: selection, pleiotropy and compensation. TREE, in press.
doi:10.1016/j.tree.2012.01.016

• we discuss evidence for variation in pleiotropy and propose the selection, pleiotropy and compensation model (SPC) for adaptive evolution
• it predicts that adaptive change in one character is associated with deleterious pleiotropy in others and subsequent selection to compensate for these pleiotropic effects
• the SPC model provides a unifying perspective for a variety of puzzling phenomena, including developmental systems drift and character homogenization
• most adaptive signatures detected in genome scans could be the result of compensatory changes, rather than of progressive character adaptations

• quantitative genetics studies the effects of genetic variation on phenotypic variation, and is thus a natural bridge between population and developmental genetics
• one of the well-established principles of developmental evolution is that genes are reused in different developmental processes
• reuse of genes causes pleiotropic effects

• directional selection will lead to the fixation of pleiotropic mutations if the advantage owing to the selected phenotypic effects outweighs the negative consequences of pleiotropic effects
• the fixed pleiotropic mutations then induce selection in favor of mutations compensating the deleterious pleiotropic effects
• adaptation by natural selection is not finished with the fixation of the advantageous alleles but entails a secondary phase of genetic change suppressing the inevitable deleterious pleiotropic effects

• developmental regulation of homologous characters is surprisingly variable
• i.e. developmental system drift
• there are many ways in which a complex character can be realized
• so a form of neutral drift takes place
• selection cannot discriminate among equivalent developmental programs
• the SPC model suggests an alternative explanation
• development of conserved characters evolves as a result of selection for compensating pleiotropic effects of adaptive allele substitutions
• under the SPC model, developmental systems drift in a conserved character can occur as a consequence of adaptive evolution of some other character
• the conserved character is likely to experience stabilizing selection at the same time as the adaptive character is under directional selection
• this combination of selection pressures is assumed to be common
• the pleiotropic effects on the character under stabilizing selection will be deleterious and thus subject to selection for rQTL that compensate for the deleterious pleiotropic effects
• these pleiotropic and compensatory genetic changes will inevitably alter the ancestral developmental process of the conserved character in one way or another, leading to a change in the development of a phenotypically conserved character
• one important implication of this hypothesis is that many genetic changes that have the statistical signature of adaptive evolution could be compensatory rather than the basis for progressive change in the phenotype
• this complicates the genomic search for genes underlying adaptive evolution
• any adaptive molecular change is more likely to be compensatory rather than adaptive
• a statistical prevalence of compensatory molecular changes over adaptive ones can also explain the high incidence of divergent cis-regulatory elements with conserved function