Limits...
A conserved mammalian protein interaction network.

Pérez-Bercoff Å, Hudson CM, Conant GC - PLoS ONE (2013)

Bottom Line: By analyzing paired alignments of orthologous and putatively interacting protein-coding genes from eight mammals, we find evidence for weak but significant co-evolution, as measured by relative selective constraint, between pairs of genes with interacting proteins.However, we find no strong evidence for shared instances of directional selection within an interacting pair.Collectively, the results suggest that, on the whole, protein interactions in mammals are under selective constraint, presumably due to their functional roles.

View Article: PubMed Central - PubMed

Affiliation: Smurfit Institute of Genetics, University of Dublin, Trinity College, Dublin, Ireland.

ABSTRACT
Physical interactions between proteins mediate a variety of biological functions, including signal transduction, physical structuring of the cell and regulation. While extensive catalogs of such interactions are known from model organisms, their evolutionary histories are difficult to study given the lack of interaction data from phylogenetic outgroups. Using phylogenomic approaches, we infer a upper bound on the time of origin for a large set of human protein-protein interactions, showing that most such interactions appear relatively ancient, dating no later than the radiation of placental mammals. By analyzing paired alignments of orthologous and putatively interacting protein-coding genes from eight mammals, we find evidence for weak but significant co-evolution, as measured by relative selective constraint, between pairs of genes with interacting proteins. However, we find no strong evidence for shared instances of directional selection within an interacting pair. Finally, we use a network approach to show that the distribution of selective constraint across the protein interaction network is non-random, with a clear tendency for interacting proteins to share similar selective constraints. Collectively, the results suggest that, on the whole, protein interactions in mammals are under selective constraint, presumably due to their functional roles.

Show MeSH
Differences between primate-specific and phylogenetically-distributed interactions. A)Gene sets used in the GO analyses of primate-specific protein interactions. There are 8876 human genes having at least one interaction (for a total of 32,916 PPIs). Among those genes, 1502 interactions (encoded by 1675 genes) are found only in primates. Of those 1675 genes, 1,521 are also involved in other, nonprimate-specific interactions, and 154 are only involved in primate specific interactions. B) Genes involved in primate-specific interactions have, on average, more total interactions (i.e., the genes involved in these interactions tend to have a higher degree k). The distribution of the difference in degree (k) for each gene in a pair of interaction proteins was compared (here referred to as ‘absolute degree difference’, Δk; x-axis). In black are the primate-specific interactions (primatePPIs) while red (dashed-line) shows the remainder of the interactions.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC3539715&req=5

pone-0052581-g002: Differences between primate-specific and phylogenetically-distributed interactions. A)Gene sets used in the GO analyses of primate-specific protein interactions. There are 8876 human genes having at least one interaction (for a total of 32,916 PPIs). Among those genes, 1502 interactions (encoded by 1675 genes) are found only in primates. Of those 1675 genes, 1,521 are also involved in other, nonprimate-specific interactions, and 154 are only involved in primate specific interactions. B) Genes involved in primate-specific interactions have, on average, more total interactions (i.e., the genes involved in these interactions tend to have a higher degree k). The distribution of the difference in degree (k) for each gene in a pair of interaction proteins was compared (here referred to as ‘absolute degree difference’, Δk; x-axis). In black are the primate-specific interactions (primatePPIs) while red (dashed-line) shows the remainder of the interactions.

Mentions: We next sought to explore the functional roles of some of the putatively recently evolved PPIs. Thus, we performed GO analyses to explore the role of the primate-specific PPIs (Methods). We first compared 1675 genes that were present in at least one primate-specific PPI (and potentially also in nonprimate PPIs; e.g., PrimPresI) to the 7201 genes that were not involved in a primate-specific PPIs (Table 2, Figure 2a). We found that the genes from PrimPresI were over-represented for biological process GO terms including “cell death,” “cell communication”, “response to stimulus,” and “macromolecule metabolic processes”, while no biological process GO terms were under-represented. Over-represented molecular functions included “protein binding,” “signal transduction activity,” “transferase activity,” and “kinase activity” while “oxidoreductase activity” was under-represented (Table 2). Using the same PPIs we also compared 154 genes involve only in primate-specific PPIs (i.e., these genes are not part of any nonprimate PPI; PrimUniqI) against the remaining 8722 genes. No GO terms were over- or under-represented in this dataset.


A conserved mammalian protein interaction network.

Pérez-Bercoff Å, Hudson CM, Conant GC - PLoS ONE (2013)

Differences between primate-specific and phylogenetically-distributed interactions. A)Gene sets used in the GO analyses of primate-specific protein interactions. There are 8876 human genes having at least one interaction (for a total of 32,916 PPIs). Among those genes, 1502 interactions (encoded by 1675 genes) are found only in primates. Of those 1675 genes, 1,521 are also involved in other, nonprimate-specific interactions, and 154 are only involved in primate specific interactions. B) Genes involved in primate-specific interactions have, on average, more total interactions (i.e., the genes involved in these interactions tend to have a higher degree k). The distribution of the difference in degree (k) for each gene in a pair of interaction proteins was compared (here referred to as ‘absolute degree difference’, Δk; x-axis). In black are the primate-specific interactions (primatePPIs) while red (dashed-line) shows the remainder of the interactions.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3539715&req=5

pone-0052581-g002: Differences between primate-specific and phylogenetically-distributed interactions. A)Gene sets used in the GO analyses of primate-specific protein interactions. There are 8876 human genes having at least one interaction (for a total of 32,916 PPIs). Among those genes, 1502 interactions (encoded by 1675 genes) are found only in primates. Of those 1675 genes, 1,521 are also involved in other, nonprimate-specific interactions, and 154 are only involved in primate specific interactions. B) Genes involved in primate-specific interactions have, on average, more total interactions (i.e., the genes involved in these interactions tend to have a higher degree k). The distribution of the difference in degree (k) for each gene in a pair of interaction proteins was compared (here referred to as ‘absolute degree difference’, Δk; x-axis). In black are the primate-specific interactions (primatePPIs) while red (dashed-line) shows the remainder of the interactions.
Mentions: We next sought to explore the functional roles of some of the putatively recently evolved PPIs. Thus, we performed GO analyses to explore the role of the primate-specific PPIs (Methods). We first compared 1675 genes that were present in at least one primate-specific PPI (and potentially also in nonprimate PPIs; e.g., PrimPresI) to the 7201 genes that were not involved in a primate-specific PPIs (Table 2, Figure 2a). We found that the genes from PrimPresI were over-represented for biological process GO terms including “cell death,” “cell communication”, “response to stimulus,” and “macromolecule metabolic processes”, while no biological process GO terms were under-represented. Over-represented molecular functions included “protein binding,” “signal transduction activity,” “transferase activity,” and “kinase activity” while “oxidoreductase activity” was under-represented (Table 2). Using the same PPIs we also compared 154 genes involve only in primate-specific PPIs (i.e., these genes are not part of any nonprimate PPI; PrimUniqI) against the remaining 8722 genes. No GO terms were over- or under-represented in this dataset.

Bottom Line: By analyzing paired alignments of orthologous and putatively interacting protein-coding genes from eight mammals, we find evidence for weak but significant co-evolution, as measured by relative selective constraint, between pairs of genes with interacting proteins.However, we find no strong evidence for shared instances of directional selection within an interacting pair.Collectively, the results suggest that, on the whole, protein interactions in mammals are under selective constraint, presumably due to their functional roles.

View Article: PubMed Central - PubMed

Affiliation: Smurfit Institute of Genetics, University of Dublin, Trinity College, Dublin, Ireland.

ABSTRACT
Physical interactions between proteins mediate a variety of biological functions, including signal transduction, physical structuring of the cell and regulation. While extensive catalogs of such interactions are known from model organisms, their evolutionary histories are difficult to study given the lack of interaction data from phylogenetic outgroups. Using phylogenomic approaches, we infer a upper bound on the time of origin for a large set of human protein-protein interactions, showing that most such interactions appear relatively ancient, dating no later than the radiation of placental mammals. By analyzing paired alignments of orthologous and putatively interacting protein-coding genes from eight mammals, we find evidence for weak but significant co-evolution, as measured by relative selective constraint, between pairs of genes with interacting proteins. However, we find no strong evidence for shared instances of directional selection within an interacting pair. Finally, we use a network approach to show that the distribution of selective constraint across the protein interaction network is non-random, with a clear tendency for interacting proteins to share similar selective constraints. Collectively, the results suggest that, on the whole, protein interactions in mammals are under selective constraint, presumably due to their functional roles.

Show MeSH