International Mammalian Genome Society

17th International Mouse Genome Conference

9-12 November 2003, Braunschweig, Germany


POSTER 34 - MAINTENANCE OF PARALOGS THROUGH SHUFFLING OF UPSTREAM REGULATORY SEQUENCES

Hafner M

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Paralogs generated through gene or genome duplication experience identical selective constraints. In the long run, one of them will thus be turned into an inactive pseudogene. To be maintained active, paralogs therefore have to gain differences, either through the gain of additional functions, by dividing the ancestral functions between the daughter genes, or through the development of different expression patterns. The core promoters of the murine BM-40 (SPARC/Osteonectin) gene and its mammalian orthologs are characterised by the presence of two homopurine stretches and two transcription start points. No similarities to promoters of amphibian or invertebrate BM-40 genes or promoters of paralogous members of the mammalian BM-40 gene family could be identified. However, promoters of mammalian androgen receptor and IGF-II genes display a similar architecture and can be aligned to the mammalian BM-40 promoters. Band shift and footprinting analyses indicated multiple SP1 binding sites within the homopurine stretches of the human BM-40 gene as has been shown for mammalian IGF-II and androgen receptor gene promoters before. Additional similarities within the first untranslated exons of BM-40 and IGF-II genes and the fact that IGF-II genes of fish display a IGF-I like exon/intron structure corroborate the hypothesis that the promoters of mammalian BM-40 and IGF-II genes are phylogenetically related. In contrast to current models of promoter evolution that assume a slow divergence of the promoters of paralogous genes, shuffling of an ancestral promoter into the upstream vicinity of unrelated genes allow a sudden change of the transcriptional regulation of the respective genes.


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