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Reassessing domain architecture evolution of metazoan proteins: major impact of errors caused by confusing paralogs and epaktologs.

Nagy A, Bányai L, Patthy L - Genes (Basel) (2011)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Institute of Enzymology, Biological Research Center, Hungarian Academy of Sciences, Budapest H-1113, Hungary. nagya@enzim.hu.

ABSTRACT
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].

No MeSH data available.


Related in: MedlinePlus

Types of homology of multidomain proteins: pseudoparalogs and epaktologs. (a) Pseudoparalogous multidomain proteins with identical DA—cytoplasmic and mitochondrial Leucyl-tRNA synthetase; (b) Pseudoparalogous multidomain proteins with different DA—cytoplasmic Leucyl-tRNA synthetase and mitochondrial Isoleucyl-tRNA synthetase; and (c) Epaktologous proteins sharing homologous domains—human neurotrypsin, human scavenger receptor cysteine-rich domain-containing group B protein, human lysyl oxidase homolog 2 and porcine deleted in malignant brain tumors 1 protein.
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f2-genes-02-00516: Types of homology of multidomain proteins: pseudoparalogs and epaktologs. (a) Pseudoparalogous multidomain proteins with identical DA—cytoplasmic and mitochondrial Leucyl-tRNA synthetase; (b) Pseudoparalogous multidomain proteins with different DA—cytoplasmic Leucyl-tRNA synthetase and mitochondrial Isoleucyl-tRNA synthetase; and (c) Epaktologous proteins sharing homologous domains—human neurotrypsin, human scavenger receptor cysteine-rich domain-containing group B protein, human lysyl oxidase homolog 2 and porcine deleted in malignant brain tumors 1 protein.

Mentions: As illustrated in Figures 1 and 2, there exists an additional category of homologous multidomain proteins that are neither orthologous (they do not have the same common ancestor in the last common ancestor of the two species), nor paralogous (they do not derive from the same gene that was duplicated within a genome), nor pseudoparalogous (neither of them were acquired by inter-species HGT): their homology is the result of shuffling of mobile domains.


Reassessing domain architecture evolution of metazoan proteins: major impact of errors caused by confusing paralogs and epaktologs.

Nagy A, Bányai L, Patthy L - Genes (Basel) (2011)

Types of homology of multidomain proteins: pseudoparalogs and epaktologs. (a) Pseudoparalogous multidomain proteins with identical DA—cytoplasmic and mitochondrial Leucyl-tRNA synthetase; (b) Pseudoparalogous multidomain proteins with different DA—cytoplasmic Leucyl-tRNA synthetase and mitochondrial Isoleucyl-tRNA synthetase; and (c) Epaktologous proteins sharing homologous domains—human neurotrypsin, human scavenger receptor cysteine-rich domain-containing group B protein, human lysyl oxidase homolog 2 and porcine deleted in malignant brain tumors 1 protein.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3927612&req=5

f2-genes-02-00516: Types of homology of multidomain proteins: pseudoparalogs and epaktologs. (a) Pseudoparalogous multidomain proteins with identical DA—cytoplasmic and mitochondrial Leucyl-tRNA synthetase; (b) Pseudoparalogous multidomain proteins with different DA—cytoplasmic Leucyl-tRNA synthetase and mitochondrial Isoleucyl-tRNA synthetase; and (c) Epaktologous proteins sharing homologous domains—human neurotrypsin, human scavenger receptor cysteine-rich domain-containing group B protein, human lysyl oxidase homolog 2 and porcine deleted in malignant brain tumors 1 protein.
Mentions: As illustrated in Figures 1 and 2, there exists an additional category of homologous multidomain proteins that are neither orthologous (they do not have the same common ancestor in the last common ancestor of the two species), nor paralogous (they do not derive from the same gene that was duplicated within a genome), nor pseudoparalogous (neither of them were acquired by inter-species HGT): their homology is the result of shuffling of mobile domains.

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Institute of Enzymology, Biological Research Center, Hungarian Academy of Sciences, Budapest H-1113, Hungary. nagya@enzim.hu.

ABSTRACT
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].

No MeSH data available.


Related in: MedlinePlus