Human Monogenic Disease Genes Have Frequently Functionally Redundant Paralogs
Figure 4
Higher purifying selections on duplicated disease genes.
Compared with non-disease genes (NDs), disease genes tend to have lower dN values with their mouse- (A) and Macaca- (B) one-to-one orthologs. Furthermore, compared with disease singletons (singlet genes or singletons refer to those that do not share significant protein sequence similarities with other human genes), duplicated disease genes tend to have lower dN values with their mouse- (C) and Macaca- (D) orthologs. The higher selective constraints on duplicated disease genes can be also seen within the human genome; for example, compared with duplicated non-disease genes (ND) of similar duplication age, disease genes tend to have lower dN values with their closest paralogs within human (E; p-value = 4×10−7, Hypergeometric Distribution test). However the same isn't true when age is omitted (F), highlighting the importance of dividing gene pairs according to their duplication age. P-values shown in the boxplots (A∼D and F) were calculated using two-sample Wilcoxon Rank Sum Test. A similar plot showing no outliers is also available in Figure S6.