208. Absence of GH-R exon 3 in marsupials and monotremes argues for a eutherian specific origin and fetal specific purpose of this domain

Abstract

Growth hormone receptor (GH-R) plays a critical role in the control of growth and metabolism in all vertebrates. GH-R consists of 9 coding exons (2–10) in all eutherian mammals, while the chicken only has 8 coding exons, and does not have an orthologous region to eutherian exon 3. To further understand the evolutionary origins of exon 3 of the GH-R we have cloned the full-length GH-R sequence in a marsupial, the tammar wallaby to determine whether exon 3 was present or absent in marsupial liver cDNA. There was no evidence for the presence of an exon 3 containing mRNA in sequence of tammar pouch young and adult livers. We next examined the genomes of the platypus (a monotreme mammal) and the grey short-tailed opossum (another marsupial). Like the tammar, the GH-R gene of neither species contained an exon 3. GH receptor can obviously function in the absence of this exon, raising speculation about the function of this domain, if any, in eutherians. A comparison of exon 3 protein sequences within 16 species of eutherian mammals showed that there was ~75% homology in the domain despite only 3 residues being identical (Leu12, Gln13 and Pro17). Interestingly, we detected greater evolutionary divergence in exon 3 sequences from species that have variants of GH or prolactin (PRL) in their placentas. These data show that exon 3 was inserted into the GH-R after the divergence of marsupial and eutherian lineages at least 130 million years ago.