What does Evolution Teach us about Nuclear Receptors?

Abstract

In this chapter we first summarise the current knowledge about the phylogenetic spec-trum of nuclear receptors (NRs). Then, we discuss how studying their diversity can be helpful to make insights about their evolution. Significant attention is paid to the evolu-tion of ligand-binding ability. Recent evolutionary and functional data have challenged the traditional concept of ligand, providing a more complex view of the mechanisms by which the transcriptional activity of NRs can be modulated. Finally, we argue that the evo-lutionary analysis of NRs has contributed to a conceptual shift of our understanding of nuclear receptors, from highly specific endocrine regulators to a promiscuous metabolic rheostat.