To assess the evolutionary importance of nonallelic (or interlocus) gene conversion for the highly polymorphic human growth hormone (GH1) gene promoter, sequence variation in this region was studied in four different ethnic groups. For 14 SNPs in the proximal GH1 promoter (535bp), 60 different haplotypes were observed in 5 7 7 individuals (15 6 Britons, 116 Spaniards, 163 West-Africans, 142 Asians). Using a novel coalescence-based statistical test, significant evidence was found in the British, Spanish, and African groups for GH1 having acted as an acceptor of gene conversion, with at least one of the four paralogous GH gene promoters serving as the donor (and specifically GH2 in the Britons and Spaniards). The average gene conversion tract length was estimated to be 84 bp. A gene conversion hotspot was identified, spanning the GH1 transcriptional initiation site (positions -6 to +25). Although these findings serve to highlight the importance of gene conversion for the recent evolution of the human GH1 promoter, its relative frequency does not appear to be related simply to the presence of specific DNA sequence motifs or secondary structures, the degree of homology between GH paralogs, the distance between them, or their transcriptional orientation. The GH1 promoter was also found to be highly polymorphic in chimpanzee but not in macaque. This may reflect the lower degree of pair-wise similarity between the GH1 promoter and its paralogs in macaque (mean, 92.0%) as compared to chimpanzee (93.5%) and human (94.0%), and hence provides further support for the idea of a threshold (perhaps around 92%) below which gene conversion is reduced or abolished.

Wolf, A., Millar, D., Caliebe, A., Horan, M., Newsway, V., Kumpf, D., et al. (2009). A gene conversion hotspot in the human growth hormone (GH1) gene promoter. HUMAN MUTATION, 30(2), 239-247 [10.1002/humu.20850].

A gene conversion hotspot in the human growth hormone (GH1) gene promoter

RICKARDS, OLGA;
2009-01-01

Abstract

To assess the evolutionary importance of nonallelic (or interlocus) gene conversion for the highly polymorphic human growth hormone (GH1) gene promoter, sequence variation in this region was studied in four different ethnic groups. For 14 SNPs in the proximal GH1 promoter (535bp), 60 different haplotypes were observed in 5 7 7 individuals (15 6 Britons, 116 Spaniards, 163 West-Africans, 142 Asians). Using a novel coalescence-based statistical test, significant evidence was found in the British, Spanish, and African groups for GH1 having acted as an acceptor of gene conversion, with at least one of the four paralogous GH gene promoters serving as the donor (and specifically GH2 in the Britons and Spaniards). The average gene conversion tract length was estimated to be 84 bp. A gene conversion hotspot was identified, spanning the GH1 transcriptional initiation site (positions -6 to +25). Although these findings serve to highlight the importance of gene conversion for the recent evolution of the human GH1 promoter, its relative frequency does not appear to be related simply to the presence of specific DNA sequence motifs or secondary structures, the degree of homology between GH paralogs, the distance between them, or their transcriptional orientation. The GH1 promoter was also found to be highly polymorphic in chimpanzee but not in macaque. This may reflect the lower degree of pair-wise similarity between the GH1 promoter and its paralogs in macaque (mean, 92.0%) as compared to chimpanzee (93.5%) and human (94.0%), and hence provides further support for the idea of a threshold (perhaps around 92%) below which gene conversion is reduced or abolished.
2009
Pubblicato
Rilevanza internazionale
Articolo
Sì, ma tipo non specificato
Settore BIO/08 - ANTROPOLOGIA
Settore BIO/18 - GENETICA
English
Con Impact Factor ISI
gene conversion; GH1; growth hormone; haplotypes; primate evolution
Wolf, A., Millar, D., Caliebe, A., Horan, M., Newsway, V., Kumpf, D., et al. (2009). A gene conversion hotspot in the human growth hormone (GH1) gene promoter. HUMAN MUTATION, 30(2), 239-247 [10.1002/humu.20850].
Wolf, A; Millar, D; Caliebe, A; Horan, M; Newsway, V; Kumpf, D; Steinmann, K; Chee, I; Lee, Y; Mutirangura, A; Pepe, G; Rickards, O; Schmidtke, J; Schempp, W; Chuzhanova, N; Kehrer Sawatzki, H; Krawczak, M; Cooper, D
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/8270
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