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. 2008 Sep 9:8:247.
doi: 10.1186/1471-2148-8-247.

Metabolic innovations towards the human lineage

Shiri Freilich  1 , Leon Goldovsky, Christos A Ouzounis, Janet M Thornton
Affiliations

Metabolic innovations towards the human lineage

Shiri Freilich et al. BMC Evol Biol. .

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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Figures

Figure 1
Figure 1
A network representation of human metabolic pathways. Layout and network construction were performed using the Biolayout software [33]. Each node represents one of the pathways from Table 2, the links between the nodes were retrieved from the KEGG database diagrams. The full names of the pathways are listed in Table 2. (A) The complete network; (B) Universal pathways; (C) The eukaryotic-, metazoan- and vertebrate-specific pathways – universal pathways are omitted for clarity.
Figure 2
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).
Figure 3
Figure 3
Phylogenetic structure of the sphingolipid metabolism pathway. Diagram construction and display conventions as in Figure 2.
Figure 4
Figure 4
Phylogenetic structure of the cholesterol biosynthesis pathway. Diagram construction and display conventions as in Figure 2.
See this image and copyright information in PMC

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