Species-specific alternative splice mimicry at the growth hormone receptor locus revealed by the lin

In humans, growth hormone receptor (GHR) tran-scripts exist in two isoforms differing by the retention(GHRfl) or exclusion (GHRd3) of exon 3, whereas in miceGHRfl is solely expressed. This species-specific expres-sion pattern is believed to result from an alternativesplice event that, on the basis of conflicting data ob-tained in humans, has been considered to be tissue-,developmentally, and/or individual-specific. To deci-pher the molecular basis of this unusual trait, we iso-lated a 6.8-kilobase fragment spanning exon 3 from in-dividuals expressing GHRfl. Sequence analysis revealedthe existence of two 99% identical retroelements flank-ing this exon. Unexpectedly, individuals expressingGHRd3 displayed a 2.7-kilobase deletion involving exon3, which most likely results from an ancestral homolo-gous recombination between the two retroelements. Thelineage of these retroelements during primate evolutionrevealed the species specificity of the GHRd3 allele.These findings led us to propose a model underlying theexistence of the sole GHRfl allele in most species. Such aretrovirus-mediated alternative splice mimicry, whichclears up several as yet unexplained phenomena (