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Reassessing Domain Architecture Evolution of Metazoan Proteins: The Contribution of Different Evolutionary Mechanisms
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Reassessing Domain Architecture Evolution of Metazoan Proteins: Major Impact of Errors Caused by Confusing Paralogs and Epaktologs

Institute of Enzymology, Biological Research Center, Hungarian Academy of Sciences, Budapest H-1113, Hungary
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Genes 2011, 2(3), 516-561; https://doi.org/10.3390/genes2030516
Received: 7 June 2011 / Revised: 8 July 2011 / Accepted: 19 July 2011 / Published: 2 August 2011
(This article belongs to the Special Issue Evolution and Structure of Proteins and Proteomes 2011)
In the accompanying paper (Nagy, Szláma, Szarka, Trexler, Bányai, Patthy, Reassessing Domain Architecture Evolution of Metazoan Proteins: Major Impact of Gene Prediction Errors) we showed that in the case of UniProtKB/TrEMBL, RefSeq, EnsEMBL and NCBI’s GNOMON predicted protein sequences of Metazoan species the contribution of erroneous (incomplete, abnormal, mispredicted) sequences to domain architecture (DA) differences of orthologous proteins might be greater than those of true gene rearrangements. Based on these findings, we suggest that earlier genome-scale studies based on comparison of predicted (frequently mispredicted) protein sequences may have led to some erroneous conclusions about the evolution of novel domain architectures of multidomain proteins. In this manuscript we examine the impact of confusing paralogous and epaktologous multidomain proteins (i.e., those that are related only through the independent acquisition of the same domain types) on conclusions drawn about DA evolution of multidomain proteins in Metazoa. To estimate the contribution of this type of error we have used as reference UniProtKB/Swiss-Prot sequences from protein families with well-characterized evolutionary histories. We have used two types of paralogy-group construction procedures and monitored the impact of various parameters on the separation of true paralogs from epaktologs on correctly annotated Swiss-Prot entries of multidomain proteins. Our studies have shown that, although public protein family databases are contaminated with epaktologs, analysis of the structure of sequence similarity networks of multidomain proteins provides an efficient means for the separation of epaktologs and paralogs. We have also demonstrated that contamination of protein families with epaktologs increases the apparent rate of DA change and introduces a bias in DA differences in as much as it increases the proportion of terminal over internal DA differences.We have shown that confusing paralogous and epaktologous multidomain proteins significantly increases the apparent rate of DA change in Metazoa and introduces a positional bias in favor of terminal over internal DA changes. Our findings caution that earlier studies based on analysis of datasets of protein families that were contaminated with epaktologs may have led to some erroneous conclusions about the evolution of novel domain architectures of multidomain proteins. A reassessment of the DA evolution of multidomain proteins is presented in an accompanying paper [1]. View Full-Text
Keywords: domain architecture; epaktologs; evolution of domain architecture; multidomain protein; Paralogs domain architecture; epaktologs; evolution of domain architecture; multidomain protein; Paralogs
MDPI and ACS Style

Nagy, A.; Bányai, L.; Patthy, L. Reassessing Domain Architecture Evolution of Metazoan Proteins: Major Impact of Errors Caused by Confusing Paralogs and Epaktologs. Genes 2011, 2, 516-561.

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