The above graph shows the time of day when clock genes peak by organ. Photos: John Hogenesch/University of Pennsyl-vania/PA WireThe above graph shows the time of day when clock genes peak by organ. Photos: John Hogenesch/University of Pennsyl-vania/PA Wire

A body-clock ‘atlas’ mapping the 24-hour activity patterns of thousands of genes has been created by scientists.

The five-year-long project is expected to provide important clues about the way drug effects may be influenced by timing – for instance, taking a medicine in the morning or at night.

The research showed that most bestselling medicinal drugs target proteins made by genes whose activity changes daily.

Timing is an important but often ignored factor in drug effectiveness, the scientists point out.

Michael Hughes, a member of the team from the University of Missouri-St Louis in the US, said: “The genome is under much more clock control than we once thought. Since only a few organs were studied previously, we were only looking under the lamppost. Now we have the most comprehensive survey to date.”

The research, conducted on mice, showed that 43 per cent of all protein-coding genes were subject to ‘circadian rhythms’, or 24-hour body clock cycles.

The liver was the most rhythmic of the 12 organs studied, having more clock-like genes than any other.

“The liver was the most rhythmic of the 12 organs studied”

Many clock genes peaked in activity during the ‘rush hours’ of transcription – the process by which the genetic code is transcribed to allow protein production – preceding dawn and dusk.

Of 100 top-selling drugs, 56 targeted genes with circadian patterns of activity. This was also true of 119 of the World Health Organisation’s list of 250 ‘essential’ medicines.

“Most of these drug targets were not known to be clock-regulated,” said co-author John Hogenesch, from the University of Pennsylvania, US.

“Many metabolising enzymes and transporters are too. Because this isn’t appreciated, few of these drugs have been evaluated for time-of-day dependent efficacy, metabolism or toxicity. Now we know which drug targets are under clock control and where and when they cycle in the body. This provides an opportunity for prospective chronotherapy.”

The research is published in the journal Proceedings of the National Academy of Sciences.

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