Fig. 1

Indirect evolution of two hormone-receptor pairs. A Steps involved in the origin and evolution of the glucocorticoid receptor (GR) which is sensitive to cortisol and the mineralocorticoid receptor (MR) which is sensitive to aldosterone. The two receptors are derived from a gene for a single ancestral receptor (AncCR) which duplicated about 450 Mya. Later, two mutations occurred in the GR receptor that made it insensitive to aldosterone. Aldosterone (Aldo) did not evolve until much later (represented by a dotted circle before it arises) but was able to bind to the MR, which had retained a form close to the ancestral receptor because a third hormone similar to aldosterone formerly activated it. From Bridgham et al. (2006), reproduced by permission of the American Association for the Advancement of Science. B The two mutations required to make the GR insensitive to aldosterone (L111Q and S106P) both make the hormone insensitive to cortisol if they occur by themselves, and it is unlikely that both arose simultaneously. This apparent problem can be explained by the fact that a third hormone, 11-deoxycorticosterone (DOC) can still bind; therefore, the receptor can still be functional (in a different manner) if the S106P mutation occurs first. From Adami (2006), reproduced by permission of the American Association for the Advancement of Science