ABSTRACT: HBII-52 small nucleolar RNAs (snoRNAs) are brain-expressed posttranscriptional modifiers of serotonin receptor 2C RNA. They are organized in a cluster of 47 highly homologous gene copies spanning 100 kb at chromosome 15q11.2. Nucleotide diversity at HBII-52 snoRNA gene cluster in African and European descent populations was analyzed via resequencing of 25 functional snoRNA gene copies. Ninety-four variants were detected, from which 74 are novel. Only 16 variants are shared between Africans and Europeans. We also report a novel Yoruba-specific copy-number variant representing a 5.2-kb polymorphic deletion and resulting in a chimerical functional snoRNA copy. In both populations, the snoRNA genes are characterized by high density of single nucleotide polymorphisms and an excess of low-frequency variants. However, the variability patterns are strictly population specific and there is an extreme divergence in allele frequencies in both resequencing and HapMap data. Several tests of neutrality strongly suggest that the observed extreme population divergence at the HBII-52 region results from positive selection in Europeans. Our analysis of HBII-52 nucleotide variability spectrum shows that gene conversion is the main factor introducing variability at the cluster. Sixty-five substitutions (69%) correspond to a paralogous sequence variant (PSV) in another copy and occur at potential gene conversion tracts of >5 bp. We detected several interparalogue gene-conversion events that involve more than one PSV, with individual frequency patterns suggestive of recurrent gene conversion. Analysis based on derived and ancestral allele distribution shows that gene conversion is at least twice more frequent than point mutations. Gene conversion is an important factor in disrupting patterns of linkage disequilibrium (LD) at short scales. Consistent with this, we detect punctual breaks of LD at gene conversion sites while the overall LD at the HBII-52 cluster is high in both study populations.
Molecular Biology and Evolution 09/2009; 26(11):2563-71. · 5.55 Impact Factor