Endocrine Abstracts

Evolution of pituitary growth hormone (GH) in mammals has generally been very slow but with short bursts of rapid change in the evolution of some groups. Such a period of rapid change occurred in the evolution of GH in primates or a primate ancestor and gave rise to the marked species specificity of human GH. By cloning and sequencing of GH genes from a prosimian, the slow loris (Nycticebus pygmaeus), and a New World monkey, the marmoset, (Callithrix jacchus) we have shown that prosimian GH is similar in sequence to pig GH while marmoset GH resembles human GH. The period of rapid change in sequence during primate evolution therefore occurred after the separation of lines leading to prosimians and higher primates and before divergence of lineages for New World monkeys and Old World monkeys/apes. Only one GH gene was found in the slow loris, as in most mammals. However a process of gene duplication has led to the presence of a cluster of 5 GH-related genes in human. Cloning and sequencing of GH-related genes in the marmoset shows the presence of a cluster of 8 such genes. Amplification and sequencing of intergene regions has allowed the ordering of genes in the cluster. The gene at the 5' end of the cluster has been identified as the putative GH gene while at least 2 of the remaining 'genes' appear to be pseudogenes. The derived amino acid sequences for mature GHs encoded by the marmoset genes were all much more similar to that of human GH (and other members of the human GH cluster) than to slow loris GH. This indicates that the process of gene duplication occurred after the rapid burst of evolution; thereafter, the rate of evolution of GH returned to the slow basal mammalian level.