Molecular evolution of growth hormone and receptor in the guinea-pig, a mammal unresponsive to growth hormone

Growth in the guinea-pig is completely unresponsive to endogenous or exogen ous growth hormone, despite the fact that the guinea-pig produces normal to high levels of growth hormone and receptor. In primates and artiodactyls, growth hormone exhibits accelerated rates of evolution that appear to be co rrelated with changes in function. Surprisingly, both guinea-pig growth hor mone and receptor exhibit slow rates of evolution similar to those seen in other mammals: implying that both proteins are as functionally conserved in the guinea-pig as in other mammals or that any loss or relaxation of funct ional constraint was very recent. However, the guinea-pig growth hormone an d receptor both exhibit a single amino acid replacement at a site known to have functional significance. Nevertheless, it is unclear whether the aberr ant nature of the guinea-pig growth hormone-growth hormone receptor axis is due to these replacements or whether it is due to a defect in post-recepto r signalling. (C) 2000 Elsevier Science B.V. All rights reserved.