DUPLICATION AND DIVERGENCE OF THE GENES OF THE ALPHA-ESTERASE CLUSTEROF DROSOPHILA-MELANOGASTER

The alpha-esterase cluster of D. melanogaster contains 11 esterase gen es dispersed over 60 kb. Embedded in the cluster are two unrelated ope n reading frames that have sequence similarity with genes encoding ubi quitin-conjugating enzyme and tropomyosin. The esterase amino acid seq uences show 37-66% identity with one another and all but one have all the motifs characteristic of functional members of the carboxyl/cholin esterase multigene family. The exception has several frameshift mutati ons and appears to be a pseudogene. Patterns of amino acid differences among cluster members in relation to generic models of carboxyl/choli nesterase protein structure are broadly similar to those among other c arboxyl/cholinesterases sequenced to date. However the alpha-esterases differ from most other members of the family in: their lack of a sign al peptide; the lack of conservation in cysteines involved in disulfid e bridges; and in four indels, two of which occur in or adjacent to re gions that align with proposed substrate-binding sites of other carbox yl/cholinesterases. Phylogenetic analyses clearly identify three simpl e gene duplication events within the cluster. The most recent event in volved the pseudogene which is located in an intron of another esteras e gene. However, relative rate tests suggest that the pseudogene remai ned functional after the duplication event and has become inactive rel atively recently. The distribution of indels also suggests a deeper no de in the gene phylogeny that separates six genes at the two ends of t he cluster from a block of five in the middle.