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Metabolic innovations towards the human lineage.

Freilich S, Goldovsky L, Ouzounis CA, Thornton JM - BMC Evol. Biol. (2008)

Bottom Line: The origins of reactions and thus entire pathways are inferred using a simple taxonomic classification scheme that describes the evolutionary course of events towards the lineage of interest.We investigate the evolutionary history of the human metabolic network extracted from a metabolic database, construct a network of interconnected pathways and classify this network according to the taxonomic categories representing eukaryotes, metazoa and vertebrates.This phylogenetic view of metabolic networks puts gene innovations within an evolutionary context, demonstrating how the emergence of a phenotype in a lineage provides a platform for the development of specialized traits.

View Article: PubMed Central - HTML - PubMed

Affiliation: The European Bioinformatics Institute, EMBL Cambridge Outstation, Wellcome Trust Genome Campus, Cambridge CB10 1SD, UK. shirifre@post.tau.ac.il

ABSTRACT

Background: We describe a function-driven approach to the analysis of metabolism which takes into account the phylogenetic origin of biochemical reactions to reveal subtle lineage-specific metabolic innovations, undetectable by more traditional methods based on sequence comparison. The origins of reactions and thus entire pathways are inferred using a simple taxonomic classification scheme that describes the evolutionary course of events towards the lineage of interest. We investigate the evolutionary history of the human metabolic network extracted from a metabolic database, construct a network of interconnected pathways and classify this network according to the taxonomic categories representing eukaryotes, metazoa and vertebrates.

Results: It is demonstrated that lineage-specific innovations correspond to reactions and pathways associated with key phenotypic changes during evolution, such as the emergence of cellular organelles in eukaryotes, cell adhesion cascades in metazoa and the biosynthesis of complex cell-specific biomolecules in vertebrates.

Conclusion: This phylogenetic view of metabolic networks puts gene innovations within an evolutionary context, demonstrating how the emergence of a phenotype in a lineage provides a platform for the development of specialized traits.

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Phylogenetic structure of the N-glycan biosynthesis pathway. The diagram was constructed according to information in the KEGG database. Each box represents a reaction and each oval box represents a pathway. The colors represent the estimated phylogenetic origin of the reactions and pathways (as listed in Table 2).
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Figure 2: Phylogenetic structure of the N-glycan biosynthesis pathway. The diagram was constructed according to information in the KEGG database. Each box represents a reaction and each oval box represents a pathway. The colors represent the estimated phylogenetic origin of the reactions and pathways (as listed in Table 2).

Mentions: Our analysis demonstrates that the conserved core of metabolism, reported to be common to all domains of life, forms a structural core component of the metabolic network (the universal pathways in Figure 1). Within the formed network, we observe that lineage-specific pathways are added to the core component of the network in two characteristic ways: with direct links, or the formation of peripheral extensions. Lineage-specific pathways which are involved in amino-acid metabolism are in all cases linked directly to the universal-core network. Lineage-specific pathways which are involved in lipid metabolism and glycan biosynthesis are in most cases clustered into a few network components which are added as external extensions to the core network of universal pathways (the sub-networks are marked in Figure 1A). Since the latter have a significant contribution to the appearance of mammalian-specific phenotypes, we have studied in detail the structure of the network formed by the reactions from these pathways. As discussed below (and demonstrated in Figures 2, 3, 4), in all these sub-networks the phylogenetic view of the pathway underlines how gradual accumulation of reactions corresponds to the appearance of lineage-specific phenotypes. The significance of these pathways to the emergence of the eukaryotic cell and the appearance of multicellular animals is further discussed below.


Metabolic innovations towards the human lineage.

Freilich S, Goldovsky L, Ouzounis CA, Thornton JM - BMC Evol. Biol. (2008)

Phylogenetic structure of the N-glycan biosynthesis pathway. The diagram was constructed according to information in the KEGG database. Each box represents a reaction and each oval box represents a pathway. The colors represent the estimated phylogenetic origin of the reactions and pathways (as listed in Table 2).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2553087&req=5

Figure 2: Phylogenetic structure of the N-glycan biosynthesis pathway. The diagram was constructed according to information in the KEGG database. Each box represents a reaction and each oval box represents a pathway. The colors represent the estimated phylogenetic origin of the reactions and pathways (as listed in Table 2).
Mentions: Our analysis demonstrates that the conserved core of metabolism, reported to be common to all domains of life, forms a structural core component of the metabolic network (the universal pathways in Figure 1). Within the formed network, we observe that lineage-specific pathways are added to the core component of the network in two characteristic ways: with direct links, or the formation of peripheral extensions. Lineage-specific pathways which are involved in amino-acid metabolism are in all cases linked directly to the universal-core network. Lineage-specific pathways which are involved in lipid metabolism and glycan biosynthesis are in most cases clustered into a few network components which are added as external extensions to the core network of universal pathways (the sub-networks are marked in Figure 1A). Since the latter have a significant contribution to the appearance of mammalian-specific phenotypes, we have studied in detail the structure of the network formed by the reactions from these pathways. As discussed below (and demonstrated in Figures 2, 3, 4), in all these sub-networks the phylogenetic view of the pathway underlines how gradual accumulation of reactions corresponds to the appearance of lineage-specific phenotypes. The significance of these pathways to the emergence of the eukaryotic cell and the appearance of multicellular animals is further discussed below.

Bottom Line: The origins of reactions and thus entire pathways are inferred using a simple taxonomic classification scheme that describes the evolutionary course of events towards the lineage of interest.We investigate the evolutionary history of the human metabolic network extracted from a metabolic database, construct a network of interconnected pathways and classify this network according to the taxonomic categories representing eukaryotes, metazoa and vertebrates.This phylogenetic view of metabolic networks puts gene innovations within an evolutionary context, demonstrating how the emergence of a phenotype in a lineage provides a platform for the development of specialized traits.

View Article: PubMed Central - HTML - PubMed

Affiliation: The European Bioinformatics Institute, EMBL Cambridge Outstation, Wellcome Trust Genome Campus, Cambridge CB10 1SD, UK. shirifre@post.tau.ac.il

ABSTRACT

Background: We describe a function-driven approach to the analysis of metabolism which takes into account the phylogenetic origin of biochemical reactions to reveal subtle lineage-specific metabolic innovations, undetectable by more traditional methods based on sequence comparison. The origins of reactions and thus entire pathways are inferred using a simple taxonomic classification scheme that describes the evolutionary course of events towards the lineage of interest. We investigate the evolutionary history of the human metabolic network extracted from a metabolic database, construct a network of interconnected pathways and classify this network according to the taxonomic categories representing eukaryotes, metazoa and vertebrates.

Results: It is demonstrated that lineage-specific innovations correspond to reactions and pathways associated with key phenotypic changes during evolution, such as the emergence of cellular organelles in eukaryotes, cell adhesion cascades in metazoa and the biosynthesis of complex cell-specific biomolecules in vertebrates.

Conclusion: This phylogenetic view of metabolic networks puts gene innovations within an evolutionary context, demonstrating how the emergence of a phenotype in a lineage provides a platform for the development of specialized traits.

Show MeSH
Related in: MedlinePlus