Patterns of DNA structural polymorphism and their evolutionary implications.

The pattern of sites within purified DNA that are highly susceptible to double-stranded cleavage by micrococcal nuclease has been analyzed in the vicinity of over 20 genes from widely separated loci in Drosophila. These genes have uniformly exhibited a distinctive organization of cleavage sites such that at early times of digestion major sites are observed in the spacer regions surrounding the genes, but not within the protein coding regions themselves. Examples examined include Drosophila genes for heat-shock proteins, cytoplasmic actin, ribosomal protein 49, alcohol dehydrogenase, Sgs 4 glue protein, and other developmentally regulated transcripts, a human beta-globin gene, and mouse alpha 3-globin pseudogene. It seems probable that this gene/spacer pattern will be a general one in the genomes of eucaryotes, but not in the genomes of procaryotes, since neither pBR322 nor phage lambda DNA display such a pattern. One observes a nonrandom spacing of strong cleavage sites in Drosophila DNA, with the most frequent intervals being 195 bp and 411 bp. Such a pattern of variation in DNA structure may have evolved to facilitate the packaging of eucaryotic DNA into chromatin.