Sixty years after "Isolating Mechanisms, Evolution and Temperature": Muller's legacy.

THE major broad achievements by the luminaries concept of genetic load (Haldane 1937; Muller 1950; Crow 1993). Other essays in the Perspectives series that of science often distract from our appreciation of their significant but narrower contributions to allied refer to Muller are Paul (1988), Lederberg (1991), Crow (1992), and Crow and Abrahamson (1997). fields. One example is Linus Pauling’s pioneering contributions to the molecular clock (Zuckerkandel and While Muller’s contributions to speciation genetics are well known to researchers in that field, they are Pauling 1965); this work is far overshadowed by his monumental explorations of the nature of chemical usually given at best brief mention elsewhere. In Carlson’s detailed biography of Muller, the only mention bonds and the structures of proteins (Hager 1995). Another example, which is the focus of this article, is of Muller’s work in speciation is a relatively brief mention of his studies on the genetic basis of sterility in Herman Joseph (H. J., Joe to his friends) Muller’s work in speciation genetics. hybrids between Drosophila melanogaster and D. simulans (Carlson 1981, pp. 280–281). In actuality, Muller, like In this perspective, I discuss the legacy of the major ideas that emanate from Muller’s 1942 article. My goal Theodosius Dobzhansky and Ernst Mayr, was one of the key architects in developing a genetic theory of is to raise the profile of Muller’s influence on speciation genetics for those more familiar with his contributions speciation (Orr 1996). Not even mentioned in Carlson’s biography is a curiin other areas of genetics. As shown below, Muller played a major role in forming the conceptual frameously titled article by Muller (1942), “Isolating mechanisms, evolution and temperature.” This article grew work of speciation genetics, including influence in topics such as evolution of hybrid incompatibilities, Halout of a symposium address Muller gave at the American Society of Zoology meetings held in Dallas, Texas, at dane’s rule, and the possibility of speciation without complete geographical isolation. the end of December 1941. The title of his article reflects the name of the symposium in which it was given: EvoluMuller’s influence on diverse areas of genetics is truly impressive. He received the Nobel Prize for an extensive tion and Temperature. Here, Muller presented a detailed review of what was known about speciation genetbody of work on mutations and their induction by X rays (Muller 1927). Muller was also an important figure ics at that time. Muller’s article, however, is more than a review. He anticipated several developments in speciain the early Drosophila group and had a tremendous influence on Morgan and Sturtevant (Carlson 1981; tion genetics that would be rediscovered five or six decades later. Although neglected by Carlson (1981) and Kohler 1994). Perhaps Muller’s most important contributions are those he made to the fundamentals of genetmost other accounts of Muller’s contributions, this article represents a foundation for research on the genetics ics—including work on the size and nature of the gene, the gene as the basis of life, the relationship between of speciation. In this commentary I discuss the legacy of the major ideas that emanate from Muller’s 1942 gene and character, and the notion that mutable autocatalysis is the essence of life (Witkin 2001). In the funcarticle. tional interpretation of allelic series, Muller’s “morphs” remain an active formalism to this day (Muller 1932). GENETIC RECOMBINATION, ISOLATION, Within evolutionary genetics, Muller was the leading AND SPECIATION advocate for the “classical” position in the classical-balance school debate (Lewontin 1974). He is also known Muller’s article begins with the provocative first sentence: “Sexual reproduction is not an unmixed blessfor his work on the evolution of sex, including the eponymous Muller’s (1964) ratchet and for developing the ing”. His point is that, while recombination provides