A network perspective on the evolution of metabolism by gene duplication.

Abstract:

BACKGROUND:Gene duplication followed by divergence is one of the main sources of metabolic versatility. The patchwork and stepwise models of metabolic evolution help us to understand these processes, but their assumptions are relatively simplistic. We used a network-based approach to determine the influence of metabolic constraints on the retention of duplicated genes. RESULTS:We detected duplicated genes by looking for enzymes sharing homologous domains and uncovered an increased retention of duplicates for enzymes catalyzing consecutive reactions, as illustrated by the ligases acting in the biosynthesis of peptidoglycan. As a consequence, metabolic networks show a high retention of duplicates within functional modules, and we found a preferential biochemical coupling of reactions that partially explains this bias. A similar situation was found in enzyme-enzyme interaction networks, but not in interaction networks of non-enzymatic proteins or gene transcriptional regulatory networks, suggesting that the retention of duplicates results from the biochemical rules governing substrate-enzyme-product relationships. We confirmed a high retention of duplicates between chemically similar reactions, as illustrated by fatty-acid metabolism. The retention of duplicates between chemically dissimilar reactions is, however, also greater than expected by chance. Finally, we detected a significant retention of duplicates as groups, instead of single pairs. CONCLUSION:Our results indicate that in silico modeling of the origin and evolution of metabolism is improved by the inclusion of specific functional constraints, such as the preferential biochemical coupling of reactions. We suggest that the stepwise and patchwork models are not independent of each other: in fact, the network perspective enables us to reconcile and combine these models.

journal_name

Genome Biol

journal_title

Genome biology

authors

Díaz-Mejía JJ,Pérez-Rueda E,Segovia L

doi

10.1186/gb-2007-8-2-r26

subject

Has Abstract

pub_date

2007-01-01 00:00:00

pages

R26

issue

2

eissn

1474-7596

issn

1474-760X

pii

gb-2007-8-2-r26

journal_volume

8

pub_type

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