Episodic evolution of protein hormones in mammals

Pituitary growth hormone (GH) and prolactin have been shown previously to d isplay 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 e xplore 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 polypep tide for analysis)-those for which sequences from at least four eutherian o rders are available with a suitable non-eutherian outgroup. Six of these (G H, prolactin, insulin, parathyroid hormone, glycoprotein hormone alpha -sub unit and luteinizing hormone beta -subunit) showed markedly variable evolut ionary 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 a nd thyroid-stimulating hormone beta -subunit) showed no significant rate va riation. Based on the sequences currently available, and pooling data from all eight proteins, the phase of slow basal change occupied about 85% of th e sampled evolutionary time, but most evolutionary change (about 62% of the substitutions accepted) occurred during the episodes of rapid change. It i s concluded that, in mammals at least, a pattern of prolonged periods of ne ar-stasis with occasional episodes of rapid change provides a better model of evolutionary change for protein hormones than the one of constant evolut ionary rates that is commonly favored. The mechanisms underlying this episo dic evolution are not yet clear, and it may be that they vary from one grou p to another; in some cases, positive selection appears to underlie bursts of rapid change. Where gene duplication is associated with a period of acce lerated 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.