Integrating the universal metabolism into a phylogenetic analysis.

The darwinian concept of "descent with modification" applies to metabolic pathways: pathways sharing similarities must have inherited them from an exclusive, hypothetical ancestral pathway. Comparative anatomy of biochemical pathways is performed using five criteria of homology. Primary homologies of "type I" were defined as several pathways sharing the same enzyme with high specificity for its substrate. Primary homologies of "type II" were defined as the sharing of similar enzymatic functions, cofactors, functional family, or recurrence of a set of reactions. Standard cladistic analysis is used to infer the evolutionary history of metabolic development and the relative ordering of biochemical reactions through time, from a single matrix integrating the whole basic universal metabolism. The cladogram shows that the earliest pathways to emerge are metabolism of amino acids of groups I and II (Asp, Asn, Glu, and Gln). The earliest enzymatic functions are mostly linked to amino acid catabolism: deamination, transamination, and decarboxylation. For some amino acids, catabolism and biosynthesis occur at the same time (Asp, Glu, Lys, and Met). Catabolism precedes anabolism for Asn, Gln, Arg, Trp, His, Tyr, and Phe, and anabolism precedes catabolism for Pro, Ala, Leu, Val, Ile, Cys, Gly, Ser, and Thr. The urea cycle evolves from arginine synthesis. Metabolism of fatty acids and sugars develops after the full development of metabolism of amino acids of groups I and II, and they are associated with the anabolism of amino acids of groups III and IV. Syntheses of aromatic amino acids are branched within sugar metabolism. The Krebs cycle occurs relatively late after the setting of metabolism of amino acids of groups I and II. One portion of the Krebs cycle has a catabolic origin, whereas the other portion has an anabolic origin in pathways of amino acids of groups III and IV. It is not possible to order glycolysis and gluconeogenesis with regard to the Krebs cycle, as they all belong to "period 6." Pentose-phosphate and Calvin cycles are later (periods 7 and 8, respectively). Cladistic analysis of the structure of biochemical pathways makes hypotheses in biochemical evolution explicit and parsimonious.

Evolution of amino acid metabolism inferred through cladistic analysis.

Because free amino acids were most probably available in primitive abiotic environments, their metabolism is likely to have provided some of the very first metabolic pathways of life. What were the first enzymatic reactions to emerge? A cladistic analysis of metabolic pathways of the 16 aliphatic amino acids and 2 portions of the Krebs cycle was performed using four criteria of homology. The analysis is not based on sequence comparisons but, rather, on coding similarities in enzyme properties. The properties used are shared specific enzymatic activity, shared enzymatic function without substrate specificity, shared coenzymes, and shared functional family. The tree shows that the earliest pathways to emerge are not portions of the Krebs cycle but metabolisms of aspartate, asparagine, glutamate, and glutamine. The views of Horowitz (Horowitz, N. H. (1945) Proc. Natl. Acad. Sci. U. S. A. 31, 153-157) and Cordón (Cordón, F. (1990) Tratado Evolucionista de Biologia, Aguilar, Madrid, Spain), according to which the upstream reactions in the catabolic pathways and the downstream reactions in the anabolic pathways are the earliest in evolution, are globally corroborated; however, with some exceptions. These are due to later opportunistic connections of pathways (actually already suggested by these authors). Earliest enzymatic functions are mostly catabolic; they were deaminations, transaminations, and decarboxylations. From the consensus tree we extracted four time spans for amino acid metabolism development. For some amino acids catabolism and biosynthesis occurred at the same time (Asp, Glu, Lys, Leu, Ala, Val, Ile, Pro, Arg). For others ultimate reactions that use amino acids as a substrate or as a product are distinct in time, with catabolism preceding anabolism for Asn, Gln, and Cys and anabolism preceding catabolism for Ser, Met, and Thr. Cladistic analysis of the structure of biochemical pathways makes hypotheses in biochemical evolution explicit and parsimonious.

Early steps of metabolism evolution inferred by cladistic analysis of amino acid catabolic pathways.

Among abiotic molecules available in primitive environments, free amino acids are good candidates as the first source of energy and molecules for early protocells. Amino acid catabolic pathways are likely to be one of the very first metabolic pathways of life. Among them, which ones were the first to emerge? A cladistic analysis of catabolic pathways of the sixteen aliphatic amino acids and two portions of the Krebs cycle is performed using four criteria of homology. The cladogram shows that the earliest pathways to emerge are not portions of the Krebs cycle but catabolisms of aspartate, asparagine, glutamate, glutamine, proline, arginine. Earliest enzymatic catabolic functions were deaminations and transaminations. Later on appeared enzymatic decarboxylations. The consensus tree allows to propose four time spans for catabolism development and corroborates the views of Cordón in 1990 about the evolution of catabolism.

Las principales etapas de la evolución del metabolismo celular. Una aproximación evolucionista al estuido del metabolismo

Todos los fenómenos biológicos son el resultado de un proceso evolutivo. El metabolismo celular no es una excepción y en las células actuales se pueden encontrar huellas de ese proceso. En este trabajo ponemos de manifiesto, a través del análisis comparado, rasgos metabólicos suficientemente significativos como para permitirnos proponer un modelo filogenético de despliegue del metabolismo celular e identificar las principales etapas del mismo. El primer modelo de este tipo fue desarrollado por F. Cordón (1990), en el contexto de su teoría de unidades de niveles de integración, y forma parte del desarrollo de la misma. El que presentamos aquí coincide plenamente con el de Cordón, pero está razonado a partir de argumentos que no son privativos de su teoría; con ello perseguimos independizar la discusión del primero de la argumentación de la segunda, de manera que la verosimilitud del modelo que proponemos, en el que se llega a las mismas conclusiones, refuerce los argumentos propios de la teoría y, como consecuencia, a ésta. (AU)