Early To Bed, Early To Rise

[Guest guest]

Early To Bed, Early To Rise

http://www.medicalnewstoday.com/medicalnews.php?newsid=52319

In an upcoming G & D paper, a team of German scientists presents a

genetic basis for understanding human morning lark behavior. Dr.

Achim Kramer (Charite Universitaetsmedizin Berlin) and colleagues

have uncovered a genetic cause for the human familial advanced sleep

phase syndrome (FASPS), which causes people to both go to sleep and

wake up very early.

" Being a morning lark or a night owl is something encoded in people's

genes and we here made substantial progress to uncover the molecular

basis for that, " explains Dr. Kramer.

FASPS is a dominantly inherited circadian rhythm disorder in which

patients' inborn biological clock (or circadian clock as it is known

by scientists) runs ahead of normal. Circadian clocks are found in

organisms ranging from bacteria to humans. They keep our bodies'

daily activities, like sleeping and eating, on a roughly 24 hour

schedule, or period. FASPS patients' periods are about 4 hours

advanced, causing the patients to retire at 6 or 7pm and rise by 4am.

In 1999, it was discovered that a mutated gene, called PERIOD2 (PER2)

is mutated in many cases of FASPS.

Dr. Kramer and colleagues mapped phosphorylation sites on the PER2

protein. They identified 21 sites, one of which (Serine 659), was

implicated in FASPS. By monitoring the bioluminescence cycles of cell

lines, the researchers demonstrated that mutation of Serine 659

causes a shortening of the luminescence period and recapitulates the

FASPS phenotype. The researchers determined that the mutated form of

Serine 659, which does not get phosphorylated, leads to PER2's

destabilization and earlier clearance from the cell nucleus.

The research team went on to show that mutations of other PER2

phosphorylation sites have differential effects on PER2 protein

stability, circadian period length, and organismal behavior. In fact,

using a simple mathematical algorithm modeled after their work, the

researchers successfully explained how different PER phosphorylation

defects result in the behaviors displayed by well-known circadian

mutants in hamsters and fruit flies.

Dr. Kramer adds that " This is the first example where the regulation

of a complex human behaviour could be really nailed down to its

genetic basis and molecular mechanism. "