How do cells come up with their programming language?

Norman Horowitz proposed the retrograde hypothesis in 1945 explaining metabolic pathway origins. Evolutionary biochemists debate pathway evolution mechanisms. Bioinformaticians reconstruct ancestral metabolic networks from comparative genomics. Systems biologists model pathway assembly dynamics.

Sam Granick proposed forward pathway evolution in 1965 studying heme and chlorophyll biosynthesis. He observed pathway intermediates retained functional capabilities suggesting they once served as end products. Biochemists studying tetrapyrrole biosynthesis found evidence supporting stepwise pathway elaboration.

Dan Tawfik extensively studied enzyme promiscuity demonstrating most enzymes catalyze multiple reactions. Shelley Copley examined promiscuous activities’ evolutionary roles. Protein engineers exploit promiscuity for directed evolution creating novel enzyme functions. Biochemists recognize promiscuity as ubiquitous rather than exceptional enzyme property.

Marvin Ycas proposed reaction modules representing enzyme families catalyzing similar chemistry. Bioinformaticians classify enzymes into EC (Enzyme Commission) numbers grouping by reaction mechanism. Comparative genomicists identify enzyme superfamilies sharing catalytic strategies despite diverse substrates. Metabolic engineers exploit modules designing synthetic pathways from well-characterized enzymatic building blocks.

Antonio Lazcano and Stanley Miller proposed the patchwork hypothesis explaining new pathway origins from pre-existing enzymes. Roy Jensen and colleagues developed the concept through studies of enzyme specificity evolution. Comparative genomicists find evidence for pathway assembly through enzyme recruitment from disparate sources.

Contemporary evolutionary biochemists synthesize multiple hypotheses recognizing pathway evolution proceeds through varied mechanisms. Antonio Lazcano and colleagues advocate integrated models acknowledging complexity. Systems biologists computationally model pathway assembly exploring multiple evolutionary routes. Experimental evolution researchers demonstrate different assembly mechanisms under varied selection pressures.