Episodic evolution of protein hormones in mammals

Pituitary growth hormone (GH) and prolactin have been shown previously to display a pattern of evolution in which episodes of rapid change are imposed on a low underlying basal rate (near-stasis). This study was designed to explore whether a similar pattern is seen in the evolution of other protein hormones in mammals. Seven protein hormones were examined (with the common alpha-subunit of the glycoprotein hormones providing an additional polypeptide for analysis)--those for which sequences from at least four eutherian orders are available with a suitable non-eutherian outgroup. Six of these (GH, prolactin, insulin, parathyroid hormone, glycoprotein hormone alpha-subunit, and luteinizing hormone beta-subunit) showed markedly variable evolutionary rates in each case with a pattern of a slow basal rate and bursts of rapid change, the precise positions of the bursts varying from protein to protein. Two protein hormones (follicle-stimulating hormone beta-subunit and thyroid-stimulating hormone beta-subunit) showed no significant rate variation. Based on the sequences currently available, and pooling data from all eight proteins, the phase of slow basal change occupied about 85% of the sampled evolutionary time, but most evolutionary change (about 62% of the substitutions accepted) occurred during the episodes of rapid change. It is concluded that, in mammals at least, a pattern of prolonged periods of near-stasis with occasional episodes of rapid change provides a better model of evolutionary change for protein hormones than the one of constant evolutionary rates that is commonly favored. The mechanisms underlying this episodic evolution are not yet clear, and it may be that they vary from one group to another; in some cases, positive selection appears to underlie bursts of rapid change. Where gene duplication is associated with a period of accelerated evolution this often occurs at the end rather than the beginning of the episode. To what extent the type of pattern seen for protein hormones can be extended to other proteins remains to be established.