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Many reports have demonstrated the existence of a positive correlation between gene pathway position and nucleotide substitution rate.
3) Other factors, such as the pathway position [34], gene compactness and gene essentiality [35] and the percentage of disordered residues of a protein [36] may have influences on the evolutionary rate of the corresponding gene, which implicitly complicated the relationship between the scale of neighbor genes and the evolutionary pattern.
These factors, therefore, are unlikely to explain the correlation between selective constraint and pathway position.
Thus, Figure 4 demonstrates that pathway position and ENC can affect ω by influencing dN.
Pathway position of all studied branches is detailed in supplementary figure S7, Supplementary Material online.
Author's response: There are no correlation was observed between pathway position and gene duplicability.
We conducted a bivariate correlation analysis using these factors, the pathway position and the dN, dS, and ω estimates.
Pathway position analysis showed that drug targets are clearly shifted towards sources of pathways, see Figure 1D.
Additionally, we conducted a modified Monte Carlo test controlling for the association between pathway position and selective constraint.
We applied a two-tailed Students t-test to determine whether pathway position or gene copy number effect SNP frequencies.
However, removing the influence of the association between pathway position and selective constraints yields equivalent results (supplementary table S18, Supplementary Material online).
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