Evolution of the growth hormone, prolactin, prolactin 2 and somatolactin family.

Growth hormone (GH), prolactin (PRL), prolactin 2 (PRL2) and somatolactin (SL) belong to the same hormone family and have a wide repertoire of effects including development, osmoregulation, metabolism and stimulation of growth. Both the hormone and the receptor family have been proposed to have expanded by gene duplications in early vertebrate evolution. A key question is how hormone-receptor preferences have arisen among the duplicates. The first step to address this is to determine the time window for these duplications. Specifically, we aimed to see if duplications resulted from the two basal vertebrate tetraploidizations (1R and 2R). GH family genes from a broad range of vertebrate genomes were investigated using a combination of sequence-based phylogenetic analyses and comparisons of synteny. We conclude that the PRL and PRL2 genes arose from a common ancestor in 1R/2R, as shown by neighboring gene families. No other gene duplicates were preserved from these tetraploidization events. The ancestral genes that would give rise to GH and PRL/PRL2 arose from an earlier duplication; most likely a local gene duplication as they are syntenic in several species. Likewise, some evidence suggests that SL arose from a local duplication of an ancestral GH/SL gene in the same time window, explaining the lack of similarity in chromosomal neighbors to GH, PRL or PRL2. Thus, the basic triplet of ancestral GH, PRL/PRL2 and SL genes appear to be unexpectedly ancient. Following 1R/2R, only SL was duplicated in the teleost-specific tetraploidization 3R, resulting in SLa and SLb. These time windows contrast with our recent report that the corresponding receptor genes GHR and PRLR arose through a local duplication in jawed vertebrates and that both receptor genes duplicated further in 3R, which reveals a surprising asynchrony in hormone and receptor gene duplications.