Estimating genetic divergence and genetic variability with restriction endonucleases.

Restriction endonucleases cut DNA at specific sites determined by the local nucleotide sequence. By comparing related DNA segments with respect to where such cuts are made, one can estimate the extent of sequence homology between the segments. Empirical methods are presented here for using these data to measure the proportion of mismatches between two sequences, the proportion of polymorphic positions in a series of sequences, or the degree of heterozygosity in a population. These methods do not require any assumptions concerning the evolutionary or population genetic processes involved. One can also use the data to calculate the precision of each of these estimates. When the positions of the cuts are not determined, these estimates can be made, using only the lengths of the resulting DNA fragments, by means of a maximum likelihood procedure. Several examples demonstrate the usefulness of these methods to study genetic differences in regions of the genome not amenable to study by other methods.