title: A gene conversion hotspot in the human growth hormone (GH1) gene promoter.
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 (535 bp), 60 different haplotypes were observed in 577 individuals (156 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.
authors.affiliation: Institut für Medizinische Informatik und Statistik, Christian-Albrechts-Universität Kiel, Kiel, Germany. wolf@medinfo.uni-kiel.de
authors.forename: Andreas
authors.initials: A
authors.lastname: Wolf
authors.forename: David S
authors.initials: DS
authors.lastname: Millar
authors.forename: Amke
authors.initials: A
authors.lastname: Caliebe
authors.forename: Martin
authors.initials: M
authors.lastname: Horan
authors.forename: Vicky
authors.initials: V
authors.lastname: Newsway
authors.forename: Dorothea
authors.initials: D
authors.lastname: Kumpf
authors.forename: Katharina
authors.initials: K
authors.lastname: Steinmann
authors.forename: Ik-Seung
authors.initials: IS
authors.lastname: Chee
authors.forename: Young-Ho
authors.initials: YH
authors.lastname: Lee
authors.forename: Apiwat
authors.initials: A
authors.lastname: Mutirangura
authors.forename: Guglielmina
authors.initials: G
authors.lastname: Pepe
authors.forename: Olga
authors.initials: O
authors.lastname: Rickards
authors.forename: Jörg
authors.initials: J
authors.lastname: Schmidtke
authors.forename: Werner
authors.initials: W
authors.lastname: Schempp
authors.forename: Nadia
authors.initials: N
authors.lastname: Chuzhanova
authors.forename: Hildegard
authors.initials: H
authors.lastname: Kehrer-Sawatzki
authors.forename: Michael
authors.initials: M
authors.lastname: Krawczak
authors.forename: David N
authors.initials: DN
authors.lastname: Cooper
mesh_terms: D000818:Animals; D005785:Gene Conversion; D006239:Haplotypes / Q000235:genetics; D019382:Human Growth Hormone / Q000235:genetics*; D006801:Humans; D008251:Macaca / Q000235:genetics; D002679:Pan troglodytes / Q000235:genetics; D010802:Phylogeny; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011401:Promoter Regions, Genetic; D012689:Sequence Homology, Nucleic Acid
chemical_list: D019382:Human Growth Hormone