CLUSTERS OF IDENTICAL NEW MUTATIONS CAN ACCOUNT FOR THE OVERDISPERSEDMOLECULAR CLOCK

Germ-cell mutations may occur during meiosis, giving rise to independe nt mutant gametes in a Poisson process, or before meiosis, giving rise to multiple copies of identical mutant gametes at a much higher proba bility than the Poisson expectation. We report that the occurrence of these early premeiotic clusters of new identical mutant alleles increa ses the variance-to-mean ratio of mutation rate (R(u) > 1). This leads to an expected variance-to-mean ratio (R(t)) of the molecular clock t hat is always greater than one and may cover the observed range of R(t ) values. Hence, the molecular clock may not be overdispersed based on this new mutational model that includes clusters. To get a better est imation of R(u) and R(t), one needs measurements of the intrageneratio n variation of reproductive success (N-i/N-e(i)), population dynamics ((k) over bar(i)), and the proportion of new mutations that occur in c lusters (r(c)), especially those formed before germ-cell differentiati on.