COMPOSITIONAL HETEROGENEITY AND PATTERNS OF MOLECULAR EVOLUTION IN THE DROSOPHILA GENOME

The rates and patterns of molecular evolution in many eukaryotic organ isms have been shown to be influenced by the compartmentalization of t heir genomes into fractions of distinct base composition and mutationa l properties. We have examined the Drosophila genome to explore relati onships between the nucleotide content of large chromosomal segments a nd the base composition and rate of evolution of genes within those se gments. Direct determination of the G + C contents of yeast artificial chromosome clones containing inserts of Drosophila melanogaster DNA r anging from 140-340 kb revealed significant heterogeneity in base comp osition. The G + C content of the large segments studied ranged from 3 6.9% G + C for a clone containing the hunchback locus in polytene regi on 85, to 50.9% G + C for a clone that includes the rosy region in pol ytene region 87. Unlike other organisms, however, there was no signifi cant correlation between the base composition of large chromosomal reg ions and the base composition at fourfold degenerate nucleotide sites of genes encompassed within those regions. Despite the situation seen in mammals, there was also no significant association between base com position and rate of nucleotide substitution. These results suggest th at nucleotide sequence evolution in Drosophila differs from that of ma ny vertebrates and does not reflect distinct mutational biases, as a f unction of base composition, in different genomic regions. Significant negative correlations between codon-usage bias and rates of synonymou s site divergence, however, provide strong support for an argument tha t selection among alternative codons may be a major contributor to var iability in evolutionary rates within Drosophila genomes.