Natural selection and genetic linkage cause DNA segments to have genealogical histories resembling those of the selected sites. When a polymorphism maintained by selection is old, it will have an island of enhanced sequence variability surrounding it, which represents a detectable ''signature of selection.'' We investigate the structure of single-nucleotide polymorphisms (SNPs) in a 20-kb interval containing the Arabidopsis thaliana disease resistance gene RPS5, a locus containing common alleles for the presence͞ absence of the entire locus. The alleles are considerably diverged at surrounding sites, indicative of an old polymorphism maintained by selection. The island of ''enhanced'' variability extends several kilobases to either side of the RPS5 deletion junction, and these SNPs are in nearly complete linkage disequilibrium with the RPS5 insertion͞deletion. At a distance of 10 kb to either side of the locus, however, we find low levels of polymorphism and the absence of linkage disequilibrium between individual SNPs and RPS5 alleles. Our results show that the interval of enhanced variability surrounding this balanced polymorphism in Arabidopsis is large enough to be readily detected, but small enough to span the focal gene and few others. For this species it should be possible to identify the complete set of genes with long-lived polymorphisms, a potentially important subset of genes segregating for functional variants.B alanced polymorphisms are mutations maintained in populations by natural selection through heterozygote advantage, frequency-dependent selection, or spatial-temporal selection of alternative alleles. In contrast to strictly advantageous or deleterious mutations, whose persistence times as polymorphisms are generally short, balanced polymorphisms can be maintained indefinitely. They are also more likely to be segregating at intermediate frequencies, where they contribute most to population variance affecting fitness. Thus, there are good reasons to be interested in identifying balanced polymorphisms in a species.Under favorable circumstances, it is possible to infer the existence of a balanced polymorphism by examining the distribution of single-nucleotide polymorphisms (SNPs) within and between alleles. The magnitude of interallelic divergence of selectively neutral mutations can be related to the age of alleles; statistical tests have been developed to determine whether the age of a polymorphism is unusually large relative to selectively neutral expectations and hence is a candidate for a balanced polymorphism (1-3). This approach does not require prior knowledge of a gene's function, and it is not restricted to coding regions.Detailed studies of SNP have been conducted in both Drosophila and humans. These studies have not identified many new candidates for balanced polymorphisms, suggesting that this form of selection may contribute relatively little to the standing crop of functional variation within a species (refs. 4-7; for alternative approaches to detecting selection, see ref. 8). How...