  A central and long-standing issue in evolutionary theory is the origin of the
biological variation upon which natural selection acts1. Some hypotheses
suggest that evolutionary change represents an adaptation to the surrounding
environment within the constraints of an organism's innate characteristics.
Elucidation of the origin and evolutionary relationship of species has been
complemented by nucleotide sequence and gene content analyses, with profound
implications for recognizing life's major domains. Understanding of
evolutionary relationships may be further expanded by comparing systemic
higher-level organization among species. Here we employ multivariate analyses
to evaluate the biochemical reaction pathways characterizing 43 species.
Comparison of the information transfer pathways of Archaea and Eukaryotes
indicates a close relationship between these domains. In addition, whereas
eukaryotic metabolic enzymes are primarily of bacterial origin, the
pathway-level organization of archaeal and eukaryotic metabolic networks is
more closely related. Our analyses therefore suggest that during the symbiotic
evolution of eukaryotes, incorporation of bacterial metabolic enzymes into the
proto-archaeal proteome was constrained by the host's pre-existing metabolic
architecture.
