Benjamin Schuster-Bockler, et al., Dosage Sensitive Shapes the Evolution of Copy-Number Varied Regions, PLoS ONE 5(3): e9474. doi:10.1371/journal.pone.0009474
Dosage sensitivity is a significant force of negative selection on regions of copy-number variation.
It has been estimated that at least 2% of the human genome is affected by structural variations, such as inversions, small insertions/deletions or large copy-number variations (CNVs).
Previous studies have already shown that the locations and functional annotations of genes in CNV regions are strongly biased. CNVs are found more often in pericentromeric and subtelomeric regions and they overlap significantly with regions of segmental duplications.
It has also observed that coy-number variability is negatively correlated with protein interaction network metrics such as connectivity and centrality.
Gene duplication and loss are key mechanisms in evolution. Historically, it was assumed in this context that most genes can be duplicated without substantial negative fitness effects.
We found that protein complex genes are enriched for known dosage sensitive genes and exhibit substantially lower expressional noise than other genes. Consequentially, we observe that dosage sensitive genes are underrepresented in CNV regions.
Genes in CNV regions have significantly more paralogs than expected by chance, while genes in protein complexes possess, on average, fewer paralogs.