LAUSR

Science sometimes progresses through the emergence of a research paradigm leveraging an innovative experimental technique to tackle age-old questions in unexpected, theoretically clever, and ultimately correct manners. Wilson and Sarich’s classic 1969 paper made just this sort of progress by integrating several kinds of molecular evidence of protein differences among humans, apes, Old World monkeys, and New World monkeys—especially evidence gathered using the novel immunological technique of micro-complement fixation (MC’F) (1). Their achievement was twofold: i) to effectively pinpoint a relatively early divergence of humans and African apes approximately 4 to 5 Mya and ii) to provide proof of concept of the power and validity of an “evolutionary clock” approach. Both results were surprising: Standard morphological and paleontological approaches had placed the human–African ape divergence at 15 to 30 Mya, while emphasizing the irregularity of character change in evolution. Allan C. Wilson and Vincent M. Sarich’s research paradigm at University of California, Berkeley, elegantly combined immunological protocol, evolutionary theory, and statistical reasoning to address deep human evolution. Although ref. 1 stands as perhaps the pinnacle article and the clearest synthetic exposition of this revolutionary molecular evolution paradigm as it was emerging in the late 1960s, the paper should be understood as channeling an interrelated set of prior articles to which Wilson and Sarich now added one more strand of evidence: amino acid differences among human, chimpanzee, gorilla, rhesus monkey, and horse hemoglobins. Thus, understanding Wilson and Sarich’s contributions requires digging deeper than 1969. In what follows, we first comment on five prior articles of interest. We then briefly cover three key practices central to Wilson and Sarich’s research program: the experimental MC’F protocol (and associated index of dissimilarity measure), the regularity test, and the mathematics of divergence time estimation. The core conceptual contribution of their research paradigm—the molecular or evolutionary clock—is subsequently presented from two points of view, a bottom–up protein point of view and a top–down tree point of view. Finally, in light of these discussions, we briefly explore the sections of ref. 1 and gesture toward the paper’s broader impact.