Genome-Wide Deserts for Copy Number Variation in Vertebrates

Most copy number variations (CNVs) are neutral, but some are deleterious and associated with various human diseases. CNVs are distributed non-randomly in vertebrate genomes, and it was recently reported that ohnologs, which are duplicated genes derived from whole genome duplication, are refractory to CNVs (Makino and McLysaght PNAS 2010). However, it is unclear what genomic factors affect the deleterious effects of CNVs and the biological significance of the biased genomic distribution of CNVs remains poorly understood. Here we show that non-ohnologs neighboring ohnologs are unlikely to have CNVs, resulting in ohnolog-rich regions (ORRs) in vertebrate genomes being CNV deserts (Makino et al. Nature Commun. 2013). Similarly, probable dosage-sensitive singletons that are unduplicated in all vertebrate lineages also repress CNVs of their immediate neighbours. In addition, long CNVs, prone to overlap genes, are less frequently observed near ohnologs. Our results suggest that the genomic location of ohnologs is a determining factor in the retention of CNVs and that dosage-balanced ohnologs are likely to cause the deleterious effects of CNVs in these regions. We propose that investigating CNV of genes in regions that are typically CNV deserts is an efficient means to find disease-related CNVs.