Emile Zuckerkandl

For the anatomist and surgeon, see Emil Zuckerkandl.

Emile Zuckerkandl (b. July 4, 1922) is an Austrian-American biologist considered one of the founders of the field of molecular evolution. He is best known for introducing, with Linus Pauling, the concept of the molecular clock, which set the stage for the neutral theory of molecular evolution.

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Life and work

Zuckerkandl was raised in Vienna, Austria in a household of intellectuals but his family moved in 1938 to Paris followed by Algiers to escape the Nazi persecution of Jews. At the end of World War II, he spent one year at the Sorbonne, then came to the United States to study physiology—earning a master's degree in 1947 from the University of Illinois, under C. Ladd Prosser—then returned to the Sorbonne to complete a Ph.D. in biology. Zuckerkandl developed a strong interest in molecular problems; his early research at a marine biology lab in Roscoff focused on the roles copper oxidases and hemocyanin in the molting cycles of crabs. In 1957, Zuckerkandl met renowned chemist Linus Pauling, whose research interests were turning toward molecular diseases and molecular evolution as an outgrowth of his activism on nuclear issues. They arranged a post-doctoral fellowship, and Zuckerkandl (now with his wife Jane) returned to the United States to work with Pauling at Caltech beginning in 1959.^[1]

Linus Pauling and the molecular clock hypothesis

Zuckerkandl's first project under Pauling (working with graduate student Richard T. Jones) was the application of new protein fingerprinting techniques—a combination of paper chromatography and electrophoresis that produced a two-dimensional pattern—to hemoglobin. The peptide fragments of hemoglobin samples from different species, partially broken down by digestive enzymes, would produce unique patterns that could be used to estimate differences in protein structure. Zuckerkandl, Jones and Pauling published a comparison of several species' hemoglobin fingerprints in 1960, observing that the level of dissimilarity of protein fingerprints corresponded roughly to the phylogenetic distance between source species. However, the method was not conducive to quantitative comparisons, so Zuckerkandl began working on the determination of the actual peptide sequence of the α and β chains of human and gorilla hemoglobin.^[2]

In 1962, Pauling and Zuckerkandl published their first paper using the molecular clock concept (though not yet by that name). Like a number subsequent collaborative papers, it was not peer-reviewed—it was an invited paper in honor of Albert Szent-Györgyi—and they intentionally took the opportunity to "say something outrageous". The paper used the number of differences in the α and β chains of hemoglobin to infer the time since the last common ancestor for a number of species, calibrated based on paleontological evidence for humans and horses. Though the paper did not provide any explanation for why amino acid differences in a protein should accumulate at a uniform rate (the essential assumption of the molecular clock), it did show that the results were fairly consistent with those of paleontologists.^[3]

In the following years, Zuckerkandl worked to refine the molecular clock. In 1963, he and Pauling coined the term "semantides" for biological sequences—DNA, RNA, and polypeptides—that hold evolutionary information and argued that such sequences could be the basis for constructing molecular phylogenies, suggesting that the molecular clock approach might be useful for other semantides besides proteins. Emanuel Margoliash's first publication of sequence data for cytochrome c allowed comparison of the rates of molecular evolution for different proteins (cytochrome c seemed to evolve faster than hemoglobin), which Zuckerkandl discussed at a 1964 conference in Bruges. Zuckerkandl also adjusted the mathematics of the clock to account for the observation that some positions in an amino acid sequence were more stable than others, and the likelihood of multiple substitutions at the same position. In September 1964, he attended the landmark Evolving Genes and Proteins symposium, where he and Pauling presented their most influential paper ("Evolutionary Divergence and Convergence in Proteins", published in the conference proceedings the following year). The paper, primarily Zuckerkandl's work, named the evolutionary clock and presented a derivation of its basic mathematical form. Though Zuckerkandl and Pauling saw the clock as compatible natural selection, it would later become the foundation of the neutral theory of molecular evolution, in which genetic drift rather than selection is the driving force of evolution at the molecular level.^[4]

Later work

In 1965, Zuckerkandl moved back to France to direct the Centre National de Recherche Scientifique. In 1971, he became the founding editor of the Journal of Molecular Evolution, and in the late 1970s became President of the Linus Pauling Institute (then in 1992 of its successor, the Institute of Molecular Medical Sciences).^[5] His recent work includes criticism of social constructionism^[6] and intelligent design.^[7]

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