Episodic evolution of protein hormones: molecular evolution of pituitary prolactin

Previous studies have shown that pituitary growth hormone displays an episodic pattern of evolution, with a slow underlying evolutionary rate and occasional sustained bursts of rapid change. The present study establishes that pituitary prolactin shows a similar pattern. During much of tetrapod evolution the sequence of prolactin has been strongly conserved, showing a slow basal rate of change (approx 0.27 × 109 substitutions/amino acid site/year). This rate has increased substantially (~12- to 38-fold) on at least four occasions during eutherian evolution, during the evolution of primates, artiodactyls, rodents, and elephants. That these increases are real and not a consequence of inadvertant comparison of paralogous genes is shown (for at least the first three groups) by the fact that they are confined to mature protein coding sequence and not apparent in sequences coding for signal peptides or when synonymous substitutions are examined. Sequences of teleost prolactins differ markedly from those of tetrapods and lungfish, but during the course of teleost evolution the rate of change of prolactin has been less variable than that of growth hormone. It is concluded that the evolutionary pattern seen for prolactin shows long periods of near-stasis interrupted by occasional bursts of rapid change, resembling the pattern seen for growth hormone in general but not in detail. The most likely basis for these bursts appears to be adaptive evolution though the biological changes involved are relatively small.