An altered gene, named “after hours” or Afh, is a variant of a gene called Fbxl3, which had not been known to have any relationship to control of the body clock that keeps our metabolism, digestion and sleep patterns in tune with the rising and setting of the sun.
Instead of following the typical 24 hour pattern, a discovery showed that some mice had body clocks that stretched to up to a 27 hour day. Closer study of the DNA from the mice revealed that those on a 27-hour-cycle had the after hours or Afh version of the Fbxl3 gene — a large family of genes that controls the breakdown of specific proteins within body cells. Specifically, the mutation, a Cys358Ser substitution in Fbxl3, an F-box protein with leucine-rich repeats, results in long free-running rhythms of about 27 hours.
The internal body clocks of mice with the after hours gene run on a longer cycle than mice that have a normal copy of the gene with the 24 hour schedule. The body clock consists of interlocked cycles of proteins that wax and wane in cells. A key protein in the loop called CRY had a delayed rate of degradation.
Also noted, the circannual body calendar is reset every summer, when increased light inhibits the production of melatonin — important in the relationship to mood.
Sofia I. H. Godinho, Elizabeth S. Maywood, Linda Shaw, Valter Tucci, Alun R. Barnard, Luca Busino, Michele Pagano, Rachel Kendall, Mohamed M. Quwailid, M. Rosario Romero, John O’Neill, Johanna E. Chesham, Debra Brooker, Zuzanna Lalanne, Michael H. Hastings, and Patrick M. Nolan. The After-Hours Mutant Mouse Reveals a Role for Fbxl3 in Determining Mammalian Circadian Period. Published online 26 April 2007 [DOI: 10.1126/science.1141138] (in Science Express Reports).
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