Department of Ecology and Evolutionary Biology, Graduate School of Life Sciences, Tohoku University, 6-3, Aramaki Aza Aoba, Aoba-ku 980-8578, Japan.
Nat Commun. 2013;4:2283. doi: 10.1038/ncomms3283.
Most copy number variations are neutral, but some are deleterious and associated with various human diseases. Copy number variations 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 copy number variations. However, it is unclear what genomic factors affect the deleterious effects of copy number variations and the biological significance of the biased genomic distribution of copy number variations remains poorly understood. Here we show that non-ohnologs neighbouring ohnologs are unlikely to have copy number variations, resulting in ohnolog-rich regions in vertebrate genomes being copy number variation deserts. Our results suggest that the genomic location of ohnologs is a determining factor in the retention of copy number variations and that the dosage-balanced ohnologs are likely to cause the deleterious effects of copy number variations in these regions. We propose that investigating copy number variation of genes in regions that are typically copy number variation deserts is an efficient means to find disease-related copy number variations.
大多数拷贝数变异是中性的，但有些是有害的，并与各种人类疾病有关。拷贝数变异在脊椎动物基因组中分布不均匀，最近有报道称，同源基因是由全基因组复制产生的重复基因，对拷贝数变异有抗性。然而，目前尚不清楚是什么基因组因素影响拷贝数变异的有害影响，以及拷贝数变异偏性基因组分布的生物学意义仍知之甚少。在这里，我们表明，同源基因附近的非同源基因不太可能发生拷贝数变异，导致脊椎动物基因组中同源基因丰富的区域成为拷贝数变异的荒漠。我们的结果表明，同源基因的基因组位置是保留拷贝数变异的决定因素，而剂量平衡的同源基因很可能导致这些区域的拷贝数变异的有害影响。我们提出，研究通常是拷贝数变异荒漠的区域中基因的拷贝数变异是发现与疾病相关的拷贝数变异的有效方法。
