Making Genetic Connections — What Mutant Flies Reveal

With the discovery of the clock gene, the sense of time, mysterious for so many centuries... could be explored as a mechanism from the inside.
— Jonathan Weiner Time, Love and Memory, 1999.

It is fitting that the first genetic links to circadian rhythms were found in the fruit fly Drosophila melanogaster, given its importance as an organism of intensive genetic investigation. The identification of the first known gene to be associated with the clock function in any organism was made by Ron Konopka and Seymour Benzer, using Drosophila. Their remarkable discovery, published in 1971, startled the scientific community. Period or per — as they named the gene they discovered — has since been found in variant form in other organisms.

The road to finding per was arduous. It entailed tracking the activity of the Drosophila to establish normal circadian cycles, painstakingly looking for aberrant or mutant flies that did not show expected circadian patterns, and then identifying the gene that was responsible.



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Video Interview — Benzer and Konopka Describe Their Breakthrough, 2000.
This interview was filmed at Seymour Benzer's office at the California Institute of Technology three decades after Ron Konopka and he identified the per gene.


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Seymour Benzer in his Lab. The test tubes most likely contain both fruit flies and food for them.


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Alfred Sturtevant — The First Genetic Map-Maker. Sturtevant, shown in his laboratory in 1960, studied with noted early geneticist Thomas H. Morgan. While a graduate student in Morgan's laboratory, Sturtevant realized that the order in which genes are arranged on chromosomes, and their distance from one another, can be derived experimentally through genetic linkage studies of fruit flies. The more closely linked two genes are, the less likely they are to become separated in subsequent generations of fruit flies. Sturtevant created a simple map showing this information. It is considered to be the very first genetic map.


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Results.
Konopka's and Benzer's fruit fly research was ground-breaking in two respects. It tied behavior to a gene, and it identified the first clock gene to be found in any species. Above: "Wings-up Flies" are mutants that keep their wings straight up and cannot fly.

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