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

Abstract

Background: 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.

Results: 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.

Conclusion: 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.

Figure 1

The extant lysine, leucine, and arginine biosynthetic routes. Evolutionary relationship between lysine, leucine, and arginine biosynthetic genes. Genes sharing the same colour and the same level are homologs. Genes coloured in white have no homolog in the metabolic routes taken into account in this work (modified from Velasco et al 2002 [19]).

Figure 2

Distribution of lysine, leucine, arginine biosynthetic genes. Histogram showing the number of lysine, leucine, and arginine biosynthetic genes possessed by Bacteria and Archaea.

Figure 3

Structure of lysine, leucine, and arginine biosynthetic routes in the Archaea H. hispanica and P. horikoshii. The lysine, leucine, and arginine biosynthetic routes in H. hispanica (a) and in P. horikoshii (b) (see references in the text). Genes sharing the same colour and the same level are homologs. Genes coloured in white have no homolog in the metabolic routes studied in this work.

Figure 4

Structure of lysine, leucine, and arginine biosynthetic routes the Eucarya S. cerevisiae and A. thaliana. The lysine, leucine, and arginine biosynthetic routes in S. cerevisiae (a) and in A. thaliana (b) (see references in the text). Genes sharing the same colour and the same level are homologs. Genes coloured in white have no homolog in the metabolic routes studied in this work.

Figure 5

Structure of lysine, leucine, and arginine biosynthetic routes in some Bacteria. The lysine, leucine, and arginine biosynthetic routes in T. thermophilus (a), in C. glutamicum (b), and in E. coli (c) (see references in the text). Genes sharing the same colour on the same level are homologs. Genes coloured in white have no homologs in the metabolic routes studied in this work.

Figure 6

A hypothetical ancestral common route for lysine, leucine, and arginine. The ancestral metabolic pathway, constituted by a restricted, unspecific set of enzymes, able to synthesize leucine, lysine, ornithine, and LL-diaminopimelate. Coloured genes are related to the extant lysine, leucine, and arginine biosynthetic ones. Dashed circles indicate more than one metabolic step. Genes coloured in white have no homologs in the metabolic routes studied in this work.

Figure 7

Evolutionary model for the assembly of lysine, leucine, and arginine biosynthetic pathways. Evolutionary model proposed to explain the evolution and the assembly of lysine, leucine, and arginine biosynthetic pathways starting from the hypothetical common route. Dashed circles indicates more than one metabolic step.

Figure 8

Phylogenetic trees. Phylogenetic trees (Neighbor Joining, 2250 Bootstrap Replicates, Complete Deletion, Poisson Correction) constructed with the sequences of LysZ, ArgB, Ask (a) and LysY, ArgC, Asd (b).