Species-specific alternative splice mimicry at the growth hormone receptor locus revealed by the lineage of retroelements during primate evolution
| Autor: | Serge Amselem, Philippe Duquesnoy, Kalotina Machinis, Michel Goossens, Jacques Pantel, Marie-Laure Sobrier |
|---|---|
| Rok vydání: | 2000 |
| Předmět: |
Primates
Retroelements Sequence analysis Molecular Sequence Data Locus (genetics) Growth hormone receptor Biology medicine.disease_cause Biochemistry Evolution Molecular Exon symbols.namesake Mice Species Specificity medicine Animals Humans Allele Cloning Molecular Molecular Biology Phylogeny Genetics Alternative splicing Molecular Mimicry Cell Biology Exons Receptors Somatotropin Molecular mimicry Alternative Splicing Retroviridae Mendelian inheritance symbols |
| Zdroj: | The Journal of biological chemistry. 275(25) |
| ISSN: | 0021-9258 |
| Popis: | In humans, growth hormone receptor (GHR) transcripts exist in two isoforms differing by the retention (GHRfl) or exclusion (GHRd3) of exon 3, whereas in mice GHRfl is solely expressed. This species-specific expression pattern is believed to result from an alternative splice event that, on the basis of conflicting data obtained in humans, has been considered to be tissue-, developmentally, and/or individual-specific. To decipher the molecular basis of this unusual trait, we isolated a 6.8-kilobase fragment spanning exon 3 from individuals expressing GHRfl. Sequence analysis revealed the existence of two 99% identical retroelements flanking this exon. Unexpectedly, individuals expressing GHRd3 displayed a 2.7-kilobase deletion involving exon 3, which most likely results from an ancestral homologous recombination between the two retroelements. The lineage of these retroelements during primate evolution revealed the species specificity of the GHRd3 allele. These findings led us to propose a model underlying the existence of the sole GHRfl allele in most species. Such a retrovirus-mediated alternative splice mimicry, which clears up several as yet unexplained phenomena (i.e. the above-mentioned expression data, the Mendelian inheritance of GHR expression patterns, and the deletion of nonconsecutive exons in growth hormone resistant patients), represents a novel physiological mechanism accounting for protein diversity between and within species. |
| Databáze: | OpenAIRE |
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