Reconstructing the diversification of alpha-esterases: Comparing the gene clusters of Drosophila buzzatii and D-melanogaster

A cluster composed of 10 active alpha-esterase genes and a pseudogene is di stributed over 60 kb in the Drosophila melanogaster genome. This paper desc ribes the corresponding cluster in Drosophila buzzatii, whose lineage diver ged from that of D. melanogaster when the subgenera Drosophila and Sophopho ra diverged about 50 Mya. With three exceptions we find that the compositio n of the cluster is conserved in the two lineages, The location of alpha E1 in D, melanogaster differs from that of its nearest relative in D. buzzati i, and alpha E4 has duplicated independently in the two lineages. The natur e of these differences indicates that a mechanism exists whereby copies of genes can be placed in opposite orientation and nonadjacent positions withi n a gene cluster, although this does not seem to be a feature of earlier ev ents in the cluster's evolution. The rates of amino acid change are not sig nificantly different between orthologs, but the rates differ sevenfold amon g paralogs, indicating that very different selective forces are acting on t he genes of the cluster. Mapping of sequence differences onto a model of th e tertiary structure of the enzymes indicates that motifs contributing to s ubstrate binding and catalysis have changed radically in the alpha E4s and suggest that this subgroup of alpha-esterases may be evolving into a substa ntially different functional niche.