Kinetic basis of spontaneous mutation. Misinsertion frequencies, proofreading specificities and cost of proofreading by DNA polymerases of Escherichia coli

Repeating members of multiple-copy sequence families display high levels of sequence homogeneity. In order to examine the rates at which this is achieved, and to compare the rates with those assessed for the ribosomal DNA and histone gene families (Coen et al., 1982, accompanying paper), we have examined the patterns of variation in the Drosophila melanogaster species subgroup for the “complex” noncoding families of high copy-number. Our analysis reveals that the evolution of some of the families has involved the gradual replacement of ancestral repeats by variant repeats, independently within each species. Hybridizations between genomes at different levels of stringency indicate the presence of two basic ancestral families (the “500” and “360” families) within the subgroup. The majority of repeats representative of these families can be characterized by restriction sites and patterns of organization that are uniquely diagnostic for each species, excepting the two most closely related species. Drosophila mauritiana and Drosophila simulans. Another family (the “180” family) is confined to the one species. Drosophila orena, with features suggestive of a more rapid origin. The wide karyotypic distribution of some members of the 500 and 180 families, revealed by hybridization in situ, shows that chromosomes are evolving in concert with respect to gradual and rapidly evolving families. The distribution of sequence and pattern variation within the subgroup shows that the time required for gradual fixation (concerted evolution) of variants within large families, distributed throughout the karyotype, is longer than that required for the smaller and chromosomally restricted families of rDNA and histone genes (Coen et al., 1982). We discuss the forces that might either accelerate or retard the fixation of variants in karyotypically dispersed families.