Clusters of Identical New Mutations Can Account for the “Overdispersed” Molecular Clock

Germ-cell mutations may occur during meiosis, giving rise to independent mutant gametes in a Poisson process, or before meiosis, giving rise to multiple copies of identical mutant gametes at a much higher probability than the Poisson expectation. We report that the occurrence of these early premeiotic clusters of new identical mutant alleles increases 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 that 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 estimation of R(u) and R(t), one needs measurements of the intrageneration variation of reproductive success (Ni/Ne(i)), population dynamics (k‒i), and the proportion of new mutations that occur in clusters (rc), especially those formed before germ-cell differentiation.