DETECTING NONNEUTRAL HETEROGENEITY ACROSS A REGION OF DNA-SEQUENCE INTHE RATIO OF POLYMORPHISM TO DIVERGENCE

Natural selection, in the form of balancing selection or selective swe eps, can result in a decoupling of the amounts of molecular polymorphi sm and divergence. Thus natural selection can cause some areas of DNA sequence to have greater silent polymorphism, relative to divergence b etween species, than other areas. It would be useful to have a statist ical test for heterogeneity in the polymorphism to divergence ratio ac ross a region of DNA sequence, one that could identify heterogeneity g reater than that expected from the neutral processes of mutation, drif t, and recombination. The only currently available test requires that a region be arbitrarily divided into sections that are compared with e ach other, and the subjectivity of this division could be problematic. Here a test is proposed in which runs of polymorphic and fixed sites are counted, where a ''run'' is a set of one or more sites of one type preceded and followed by the other type. ?The number of runs is small er than otherwise expected if polymorphisms are clumped together. By s imulating neutral evolution and comparing the observed number of runs to the simulations, a statistical test is possible which does not requ ire any a priori decisions about subdivision.