Interparalog gene conversion pattern and evolutionary dynamics of HBII-52 C/D box snoRNAs cluster at 15q11-q12. M. Ogorelkova1, A. Navarro2, X. Estivill1. 1) Gene & Disease Prog, Ctr Genomic Regulation, Barcelona, Catalonia, Spain; 2) Experimental and Health Sciences Department, Pompeu Fabra University, Barcelona, Catalonia, Spain.
Brain expressed, paternally imprinted C/D box HBII-52 snoRNAs are organized in a ~100 Kb cluster of 47 copies on chromosome 15q11-q12. They are suggested to post-transcritionally modify the 5HT2C transcripts by affecting the editing and/or alternative splicing. The HBII-52 copies share high homology with each other (>97%), and over half of them are expected to be functionally active. Due to high level of sequence identity, gene conversion is anticipated to be the main event shaping the DNA variability of the cluster. We have analysed the DNA variability of 25 presumably functional copies in 70 Spanish individuals. In 6.6 Kb of sequence, 34 SNPs and rare variants have been identified, 23 of which are novel. Two third of the variants have minor allele frequency less than 5%. Six variants are predicted to lead to non-functional snoRNA copies. Twenty six substitutions correspond to paralogous sequence variants (PSVs) in other copies and occur at potential gene conversion sites with tract of >5 bp. We detected 4 gene conversion events involving more than one PSV, with potential tracts between 6 and 31 bp. The overall nucleotide diversity of the cluster (4.2x10 -4) is higher than the genome average, and several snoRNA copies display very high nucleotide diversity of up to 1x10 -3. Interparalog gene conversion is expected to generate excess of sequence diversity, with excess of variants with low MAF. The spectrum of variability at HBII-52 snoRNAs cluster is strongly suggestive of frequent and recurrent gene conversion events between paralogous copies, and multiple gene conversion hot spots. Multiple SNPs are found at the proximal and distal parts of the snoRNAs cluster while central copies are devoid of variants. A recent positive selection event, possibly a fixation of human-specific copy 38, might have removed the variability within the central copies, as confirmed by tests of neutrality on preliminary data. Alternatively, some snoRNA paralogs might represent gene conversion receiver hot spots.