TY - JOUR
T1 - Understanding protein evolutionary rate by integrating gene co-expression with protein interactions
AU - Pang, Kaifang
AU - Cheng, Chao
AU - Xuan, Zhenyu
AU - Sheng, Huanye
AU - Ma, Xiaotu
N1 - Funding Information:
XM is supported by NIH grant HG001696 to Michael Q Zhang. The authors greatly appreciate the comments from the three anonymous reviewers, which have significantly improved this manuscript. We thank Yangbo He for suggestions on calculating the percent variance when controlling for confounding variable.
PY - 2010/12/30
Y1 - 2010/12/30
N2 - Background: Among the many factors determining protein evolutionary rate, protein-protein interaction degree (PPID) has been intensively investigated in recent years, but its precise effect on protein evolutionary rate is still heavily debated.Results: We first confirmed that the correlation between protein evolutionary rate and PPID varies considerably across different protein interaction datasets. Specifically, because of the maximal inconsistency between yeast two-hybrid and other datasets, we reasoned that the difference in experimental methods contributes to our inability to clearly define how PPID affects protein evolutionary rate. To address this, we integrated protein interaction and gene co-expression data to derive a co-expressed protein-protein interaction degree (ePPID) measure, which reflects the number of partners with which a protein can permanently interact. Thus, irrespective of the experimental method employed, we found that (1) ePPID is a better predictor of protein evolutionary rate than PPID, (2) ePPID is a more robust predictor of protein evolutionary rate than PPID, and (3) the contribution of ePPID to protein evolutionary rate is statistically independent of expression level. Analysis of hub proteins in the Structural Interaction Network further supported ePPID as a better predictor of protein evolutionary rate than the number of distinct binding interfaces and clarified the slower evolution of co-expressed multi-interface hub proteins over that of other hub proteins.Conclusions: Our study firmly established ePPID as a robust predictor of protein evolutionary rate, irrespective of experimental method, and underscored the importance of permanent interactions in shaping the evolutionary outcome.
AB - Background: Among the many factors determining protein evolutionary rate, protein-protein interaction degree (PPID) has been intensively investigated in recent years, but its precise effect on protein evolutionary rate is still heavily debated.Results: We first confirmed that the correlation between protein evolutionary rate and PPID varies considerably across different protein interaction datasets. Specifically, because of the maximal inconsistency between yeast two-hybrid and other datasets, we reasoned that the difference in experimental methods contributes to our inability to clearly define how PPID affects protein evolutionary rate. To address this, we integrated protein interaction and gene co-expression data to derive a co-expressed protein-protein interaction degree (ePPID) measure, which reflects the number of partners with which a protein can permanently interact. Thus, irrespective of the experimental method employed, we found that (1) ePPID is a better predictor of protein evolutionary rate than PPID, (2) ePPID is a more robust predictor of protein evolutionary rate than PPID, and (3) the contribution of ePPID to protein evolutionary rate is statistically independent of expression level. Analysis of hub proteins in the Structural Interaction Network further supported ePPID as a better predictor of protein evolutionary rate than the number of distinct binding interfaces and clarified the slower evolution of co-expressed multi-interface hub proteins over that of other hub proteins.Conclusions: Our study firmly established ePPID as a robust predictor of protein evolutionary rate, irrespective of experimental method, and underscored the importance of permanent interactions in shaping the evolutionary outcome.
UR - http://www.scopus.com/inward/record.url?scp=78650594646&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=78650594646&partnerID=8YFLogxK
U2 - 10.1186/1752-0509-4-179
DO - 10.1186/1752-0509-4-179
M3 - Article
C2 - 21190591
AN - SCOPUS:78650594646
VL - 4
JO - BMC Systems Biology
JF - BMC Systems Biology
SN - 1752-0509
M1 - 179
ER -