Given that most microsatellite arrays are of no obvious functional sig
nificance, it is natural to ask how long these sequences persist durin
g evolution. The expected persistence time was calculated for microsat
ellite arrays undergoing replication slippage and random genetic drift
using diffusion theory and Monte Carlo simulation. In each of the thr
ee models of replication slippage compared, copy number changes involv
e only single steps. In one model, the rates of addition or loss of re
peat units are constant; in the other two models, they are dependent o
n array length in a linear or quadratic way. For all three models, it
was found that persistence time of microsatellite loci increases with
population size in a sublinear fashion. A heuristic argument is presen
ted as to why this result holds true for a more general class of mutat
ion mechanisms, including models that incorporate base substitutions i
n addition to replication slippage. This suggests that the approximate
ly 30% deficiency of microsatellite loci on chromosome X (relative to
autosomes) that has been well documented for several mammalian species
cannot be explained by the fact that the X chromosome has a smaller e
ffective population size than do autosomes, as has been hypothesized.