  Aquifex aeolicus is a deep-branching hyperthermophilic chemoautotrophic
bacterium restricted to hydrothermal vents and hot springs. These
characteristics make it an excellent model system for studying the early
evolution of metabolism. Here we present the whole-genome metabolic network of
this organism and examine in detail the driving forces that have shaped it. We
make extensive use of phylometabolic analysis, a method we recently introduced
that generates trees of metabolic phenotypes by integrating phylogenetic and
metabolic constraints. We reconstruct the evolution of a range of metabolic
sub-systems, including the reductive citric acid (rTCA) cycle, as well as the
biosynthesis and functional roles of several amino acids and cofactors. We show
that A. aeolicus uses the reconstructed ancestral pathways within many of these
sub-systems, and highlight how the evolutionary interconnections between
sub-systems facilitated several key innovations. Our analyses further highlight
three general classes of driving forces in metabolic evolution. One is the
duplication and divergence of genes for enzymes as these progress from lower to
higher substrate specificity, improving the kinetics of certain sub-systems. A
second is the kinetic optimization of established pathways through fusion of
enzymes, or their organization into larger complexes. The third is the
minimization of the ATP unit cost to synthesize biomass, improving
thermodynamic efficiency. Quantifying the distribution of these classes of
innovations across metabolic sub-systems and across the tree of life will allow
us to assess how a tradeoff between maximizing growth rate and growth
efficiency has shaped the long-term metabolic evolution of the biosphere.
