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This article is part of the supplement: Second Congress of Italian Evolutionary Biologists (First Congress of the Italian Society for Evolutionary Biology)

Open Access Research

The primordial metabolism: an ancestral interconnection between leucine, arginine, and lysine biosynthesis

Marco Fondi1, Matteo Brilli1, Giovanni Emiliani2, Donatella Paffetti2 and Renato Fani1*

Author Affiliations

1 Dipartimento di Biologia Animale e Genetica, Università di Firenze, Via Romana 17\19, Firenze, Italia

2 Dipartimento di Scienze e Tecnologie Ambientali Forestali, Università di Firenze, Via S. Bonaventura 13, Firenze, Italia

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BMC Evolutionary Biology 2007, 7(Suppl 2):S3  doi:10.1186/1471-2148-7-S2-S3

Published: 16 August 2007



It is generally assumed that primordial cells had small genomes with simple genes coding for enzymes able to react with a wide range of chemically related substrates, interconnecting different metabolic routes. New genes coding for enzymes with a narrowed substrate specificity arose by paralogous duplication(s) of ancestral ones and evolutionary divergence. In this way new metabolic pathways were built up by primordial cells. Useful hints to disclose the origin and evolution of ancestral metabolic routes and their interconnections can be obtained by comparing sequences of enzymes involved in the same or different metabolic routes. From this viewpoint, the lysine, arginine, and leucine biosynthetic routes represent very interesting study-models. Some of the lys, arg and leu genes are paralogs; this led to the suggestion that their ancestor genes might interconnect the three pathways. The aim of this work was to trace the evolutionary pathway leading to the appearance of the extant biosynthetic routes and to try to disclose the interrelationships existing between them and other pathways in the early stages of cellular evolution.


The comparative analysis of the genes involved in the biosynthesis of lysine, leucine, and arginine, their phylogenetic distribution and analysis revealed that the extant metabolic "grids" and their interrelationships might be the outcome of a cascade of duplication of ancestral genes that, according to the patchwork hypothesis, coded for unspecific enzymes able to react with a wide range of substrates. These genes belonged to a single common pathway in which the three biosynthetic routes were highly interconnected between them and also to methionine, threonine, and cell wall biosynthesis. A possible evolutionary model leading to the extant metabolic scenarios was also depicted.


The whole body of data obtained in this work suggests that primordial cells synthesized leucine, lysine, and arginine through a single common metabolic pathway, whose genes underwent a set of duplication events, most of which can have predated the appearance of the last common universal ancestor of the three cell domains (Archaea, Bacteria, and Eucaryotes). The model proposes a relative timing for the appearance of the three routes and also suggests a possible evolutionary pathway for the assembly of bacterial cell-wall.