Research News

The carp Phreatichthys andruzzii has been living in subterranean water-filled caves underneath the Somali desert for millions of years and has completely lost its eyes and scales. Photo: KIT
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Listen to the full-length interview with Nick Foulkes (in English, duration approx. 40 minutes) about inner clocks, fish as ideal model organisms and evolution:
[MP3] Interview with Nick Foulkes
Media reports:
How the Internal Clock is Being Lost
The internal or biological clock tells the organism when it is advantageous to look for food and when the body needs rest. It is controlled by certain genes, but is continuously readjusted by light. Because a day on Earth has 24 hours, this biological clock features the same rhythm in almost all living organisms. Yet there are exceptions:
For instance, the blind cave fish Phreatichthys andruzzii. He has been living completely isolated from the light of day in subterranean lakes underneath the Somali desert for about 2.6 million years. Over the course of these millions of years it has lost its colour, its scales and eyes and it is very probable that it now is slowly losing its biological clock. The research group around Prof. Dr Nick Foulkes at the KIT's Institute of Toxicology has investigated this issue in cooperation with Prof. Dr Cristiano Bertolucci from the University of Ferrara in Italy.
The "biological clock" of this blind fish runs for twice the usual time span.
The researchers compared the Somali cave fish with zebra fish, close relatives of Phreatichthys andruzzii. Almost half a million zebra fish live in the water tanks at Foulkes' Institute. Their genome has been decoded already and genetically altered, new lines can be created easily. Whereas zebra fish synchronise their circadian rhythm with cycles of darkness and light like all organisms, the cave fish do not react to light at all anymore. Left in peace, they behave as if their day had about 47 hours.
They can be influenced by food at certain times and in this they prove very flexible. The Somali cave fish seem indifferent to whether they get new food every ten hours or only every sixty hours. They can survive completely without food for up to three weeks. In such an event, they slow down their already rather slow metabolism even further and reduce consumption to the minimum. Time seems to pass slower for them in general, for even at more than forty years of age they are just as fast as their offspring, display hardly any signs of ageing and even continue to lay eggs. "These fish reveal to us how the inner clock has been lost in the course of evolution. If we look again at them in a few million years, they may have no trace of a circadian rhythm. Perhaps such a mechanism simply does not present them with a significant chance of survival in their subterranean habitat", says Nick Foulkes.
Zebra Fish as a Comparison
The researchers are particularly interested in the molecular building blocks of the biological clock, which prove to be very similar in all organisms. Here, they are targeting several groups of genes. For instance, they have inserted light sensitive zebra fish genes into the cells of cave fish. Equipped with these genes, the blind cave fish suddenly revealed themselves to be influenced by light in their activity. "We now intend to decode the cave fish genome and to compare it with that of the zebra fish in order to determine in greater detail which mutations are responsible for slowing down the biological clock", says Foulkes.
Reindeer Likewise Have a Different Rhythm
Foulkes explains that such processes can be observed also in some mammals. For instance, in reindeer living north of the Arctic Circle. In summer, they actively search for food almost around the clock, whereas in winter they live in perpetual darkness. The biological clock of these animals may have considerably weakened in impact in the course of evolution, because a rigid rhythm of day and night does not offer any advantage in the region of the Arctic Circle.
Living Against the Clock Weakens the Immune System
Humans, however, only had a few millennia to adapt to extreme seasons or modern life with shift work and distance travel across time zones. Living against one's inner clock is not only exhausting but also unhealthy. In the long run, a mode of living in opposition to the activity rhythm set down in the cells weakens the immune system, increasing the susceptibility to viruses and even cancer. "People ought to go to sleep when they get tired and rise only when they are well-rested", says Foulkes. Yet the researchers themselves often spend all day at the laboratory.

