We have used the method of disequilibrium pattern analysis to
examine associations between the
threonine-glycine (Thr-Gly) encoding repeat region of the clock gene
period (per) of Drosophila
melanogaster, and polymorphic sites both upstream and downstream of
the repeat, in a number of
European fly populations. The results are consistent with the view that
selection may be operating
on various haplotypes which share the Thr-Gly length alleles encoding
17, 20 and 23 dipeptide
pairs, and that the repeat itself may be the focus for selection.
These conclusions lend support to a
number of other population and behavioural investigations which
have provided evidence that
selection is acting on the Thr-Gly region. The linkage analysis was
also used to infer an approximate mutation rate (μ) for the repeat, of
10−5<μ<4×10−5
per gamete per generation.
Direct measurements of the mutation rate using the polymerase chain
reaction in a pedigree
analysis of tens of thousands of individuals do not contradict this
value. Consequently, the Thr-Gly repeat does not have a mutation rate
that is as high as some of the non-coding minisatellites,
but it is several orders of magnitude higher than the nucleotide
substitution rate. The implications
of this elevated mutation rate for linkage disequilibria and selection are discussed.