Ronald Konopka: pioneer of genetic chronobiology

Ronald KonopkaA lovely whiff of summer is floating through the UK this week, marking the beginning of the most frantic holiday season of the year. Soon, we will be packing up our beach towels and head off to the airport, to fly to the Azores, or Cuba, or even Hawaii, or another island of our winter dreams. And as we move around the globe, our sense of time will be challenged: while the Azores are only 1 hour later than Britain, time in Cuba lags 5 hours behind, and Hawaii lags behind by almost half a day (11 hours). These time differences are responsible for the different degrees of jet lag that we experience. It was the ground-breaking work of Ronald Konopka more than 50 years ago in the field of chronobiology – the biology of the sense of time – that helps us to understand these effects.

Our bodies are accustomed to a 24 hour rhythm, which is why even a trip to the Azores, or the half-yearly time change of plus/minus 1 hour can throw some of us off balance for days.

Our inner clocks introduce a temporal hierarchy to our bodily processes, ensuring that hunger-inducing and sleep-inducing hormones are produced at appropriate times of the day and that, for example, we do not get hungry, while we are preparing to go to sleep.

Back in the 1950’s, the early chronobiologists Gustav Kramer and Jürgen Aschoff at the Max Planck Institute for Behavioural Physiology found that humans living in bunkers under constant light conditions slow their day/night or circadian rhythm from 24 hours to about 25 hours over time and then retain this period of 25 hours.

So there is something in our bodies that gives it a quasi-daily rhythm even in the absence of daylight cues. And this is not only true of us, but of all organisms studied to far – plants close their flowers and hug in their leaves periodically, usually during the night, and will continue to do so if left in constant light.

In 1967, a young graduate student, Ronald Konopka, joined the lab of Seymour Benzer, the grandfather of behavioural genetics, at Caltech to study the genetic driving forces that govern circadian rhythm, or the sense of time. The idea that genes can have a direct and directed impact on particular behaviours was extremely controversial at the time. Many researchers held that behaviour was too complex to be governed by single genes.

It was the work of Ronald Konopka that eventually proved that our circadian rhythm can be traced back to our genes.. Benzer and Konopka worked with a small, versatile laboratory animal – the fruit fly. The latin name for fruit fly is Drosophila, or “dew lover”, in reference to the fact that their activity peaks just after dawn. Even the timing of their emergence from the pupal case is centered around the morning hours. Konopka randomly mutated the genome of these flies, bred their children, and waited for each family line to emerge from the pupal case to test the timing of their inner clocks.

It took 200 family lines until the first clock mutant was found: a family line that emerged at all times of the day, instead of the morning only. Further cousins were found that emerged always too early, and other cousins would emerge too late. And this activity pattern persisted throughout the life of these flies. In other words, some cousins had no daily periodicity at all, some had short periods and others had long periods. Konopka succeeded in tracing all three changes in rhythmicity to the same gene locus, appropriately named period. This research was published in a seminal paper in 1968. It marked the finding of the first gene that shaped a particular behaviour.

We now know that period encodes for a protein that is at the heart of the body’s master clock in fruit flies, and that the mechanics of this master clock are, in principle, conserved in plants, and even humans. The relevance of Konopka’s finding cannot be overstated: Generally, it proved the concept that there are particular genes that shape a particular behaviour. Specifically, it proved that the mechanics that govern behaviour as complex and as pervasive as the sense of time can be dissected down to the level of single genes in a manner that is conserved across species.

Konopka continued to work on the mechanics of the master clock, and also devoted a lot of his time to teaching.

Dr Ronald Konopka sadly passed away in February this year.

Anne Petzold is a second year PhD student studying Life Sciences

Image: Ron Konopka memorial page 

 

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