Molecular evolution of GH in primates: characterisation of the GH genes from slow loris and marmoset defines an episode of rapid evolutionary change

Pituitary growth hormone (GH), like several other protein hormones, shows a n unusual episodic pattern of molecular evolution in which sustained bursts of rapid change are imposed on long periods of very slow evolution (near-s tasis). A marked period of rapid change occurred in the evolution of GH in primates or a primate ancestor, and gave rise to the species specificity th at is characteristic of human GH. We have defined more precisely the positi on of this burst by cloning and sequencing the GH genes for a prosimian, th e slow loris (Nycticebus pygmaeus) and a New; World monkey, marmoset (Calli thrix jacchus). Slow loris GH is very similar in sequence to pig GH, demons trating that the period of rapid change occurred during primate evolution, after the separation of lines leading to prosimians and higher primates. Th e putative marmoset GH is similar in sequence to human GH, demonstrating th at the accelerated evolution occurred before divergence of New World monkey s and Old World monkeys/apes. The burst of change was confined largely to c oding sequence for mature GH, and is not marked in other components of the gene sequence including signal peptide, 5' upstream region and introns. A n umber of factors support the idea that this episode of rapid change mas due to positive adaptive selection. Thus (1) there is no apparent loss of func tion of GH in man compared with non-primates, (2) after the episode of rapi d change the rate of evolution fell towards the slow basal level that is se en for most mammalian GI-Is, (3) the accelerated rate of substitution for t he exons of the GH gene significantly. exceeds that for introns, and (3) th e amino acids contributing to the hydrophobic core of GH are strongly conse rved when higher primate and other GH sequences are compared, and for codin g sequences other than that coding for hydrophobic core residues the rate o f substitution for non-synonymous sites (K-A) Is significantly greater than that fur synonymous sites (K-S) In slow loris, as in most non-primate mamm als, there is no evidence for duplication of the GH gene, but in marmoset, as in rhesus monkey and man, the putative GH gene is one of a cluster of cl osely related genes.