This Week's Citation Classic is Henry J. Vogel. 1964. Distribution of Lysine Pathways Among Fungi: Evolutionary Implications. The American Naturalist, Vol. 98, No. 903.
Francois Jacob and Jacques Monod are frequently credited with discovering "repressors" of gene expression. While they did come up with the operon model of gene regulation, it's not precisely true that they were the first to consider "repression" as a means of gene regulation.
In fact, the first repressor, the arginine repressor, was independently discovered by Henry Vogel and Werner Maas (see Maas 1994). This is enough to give any man lasting fame. However, in my estimation, this is not the greatest of Vogel's accomplishments. Even more worthy is the study described in The American Naturalist, Distribution of Lysine Pathways Among Fungi: Evolutionary Implications.
This study was one of the first attempts to resolve the phylogenetic relationships of organisms based on knowledge their metabolic pathways.
Vogel was the first to discover that there were two alternative pathways to synthesize lysine. One route starts from a-aminoadipic acid (AAA) while the other uses diaminopimelic acid (DAP) as a precursor. These lysine biosynthesis pathways are mutually exclusive in their occurrence.
"The two paths of lysine synthesis seem to be quite unusual in the consistency of their dichotomous distribution over a broad range of biological forms. This consistency suggests that these paths did not arise sporadically, and that their distribution pattern was not disturbed by genetic exchange. It appears probable that neither path emerged in an organism possessing the other, since a partial appearance of either path in the presence of the other may well have been selected against, and an appearance in toto is thought unlikely in view of the number of enzymes involved in each path. It is thus assumed that the two lysine paths arose individually in organisms incapable of lysine synthesis."
Vogel realized that, like any phenotype, these alternative forms could be used to dissect the evolutionary history of the fungi. Using C14 tracers, Vogel could determine which fungus used which lysine pathway.
"The general procedure consisted in allowing the organisms to utilize selected C14-labeled compounds, and measuring the relative specific radioactivity of the lysine, threonine, and aspartic acid from the protein of the cultures obtained, The radiocarbon tracers used were 3- and 4-labeled aspartic acids, 1-labeled alanine, and 2-labeled acetate. With these tracers, the mode of lysine synthesis is revealed through characteristic labeling patterns (cf. Vogel, 1959)."
Vogel found that,
"The labeling pattern corresponding to the a-aminoadipic acid-lysine path was given by all basidiomycetes and ascomycetes and by those phycomycetes which produce non-flagellate or posteriorly uniflagellate spores. The pattern characteristic of the a-e diiaminopimelic acid-lysine path was shown by those phycomycetes which produce anteriorly uniflagellate or biflagellate spores."
Vogel concluded his paper by writing,
"A common evolutionary precursor of organisms having the a-aminoadipic acid path is postulated; these organisms include euglenids as the only non-fungal forms known to have this path. The inferred common precursor is viewed as a lysine-non-producing, animal-like organism in an evolutionary line that had branched off the main stream of evolution of the plant kingdom."
Naturally today we would infer evolutionary relationships from genetic sequences, but back in the day, comparative morphology was the rule. Vogel's study was groundbreaking in that he expanded the purview of the phylogeneticists to include biochemistry and metabolism as an additional means to tease out the evolutionary history of organisms. For the most part, his phylogenetic conclusions have withstood the test of time. Quite clever indeed.