Ronald J. Konopka (1947–2015)

Ronald J. Konopka Ron Konopka was found dead of an apparent heart attack in his Pasadena, CA home on February 14, 2015. Konopka was my close contemporary and began graduate school at Caltech in 1967. He published his thesis work along with his mentor Seymour Benzer in what is perhaps the single most influential paper in circadian rhythms (Konopka and Benzer, PNAS 68, 2112–2116). The field has spent much of the subsequent 45 years deciphering the meaning and validating (over and over again) the importance of this Rosetta stone. It began the modern era of circadian biology and is the cornerstone of my own circadian career. As if this were not enough, it is arguably the landmark paper in behavioral genetics writ large. Benzer moved from Purdue to Caltech in the mid-60s and began this field; the physical move paralleled an intellectual move from prokaryotic genes to the underpinnings of behavior. He is properly credited with combining simple behavioral screens with the power ofDrosophila genetics. The strategy could associate single mutations and the underlying genes with a behavioral phenotype. Although Benzer accumulated a coterie of talented students and post-docs to join him in this grand adventure, Konopka was the first. Moreover, he brought the circadian problem to Benzer rather than vice versa, and Ron designed as well as carried out the primary screen used to search for circadian mutants. The clock causes adult flies to eclose (emerge from the pupal case) at or shortly after dawn; this rhythmic emergence continues in constant darkness, with about 24 hr periodicity. The screen therefore searched for mutant flies that eclose in aberrant fashion and was remarkably successful. Ron found a short period mutant (about 20 hr), a long period mutant (about 30 hr) and an arrhythmic mutant. Three striking features of the 1971 Konopka and Benzer paper led them to propose that the mutants were central to circadian rhythms. First, the three mutants affected not only the eclosion rhythm but also an independent circadian rhythm feature, locomotor activity, which also exhibited a short period, a long period, or arrhythmicity. Second, genetic analysis indicated that all three mutations were alleles of a single gene, which they named period. The more expected result would have been three different genes each giving rise to the very different circadian phenotypes of fast, slow, or no rhythm; the finding of a single gene suggested that only a small number of gene products might be running the circadian clock. Third and most intriguingly, the results indicated that this single protein was of key importance for circadian timing, as it could mutate to a fast-running protein (short period) or a slow-running protein (long period) as well as being necessary for rhythmicity. It took another 15 years for recombinant DNA and DNA sequencing to allow molecular characterization of the period gene and its protein, which verified some of these much earlier implications. For example, the short and long period alleles were determined to be missense mutations that altered the protein, whereas the arrhythmic mutation was a stop codon that prevented synthesis of the protein. Subsequent dynamic assays