NUCLEOTIDE VARIATION IN THE TRIOSEPHOSPHATE ISOMERASE (TPI) LOCUS OF DROSOPHILA-MELANOGASTER AND DROSOPHILA-SIMULANS

DNA sequence variation in a 1.1-kb region including the coding portion of the Tpi locus was examined in 25 homozygous third-chromosome lines of Drosophila melanogaster, nine lines of Drosophila simulans, and on e line of Drosophila yakuba. Our data show that the widespread allozym e polymorphism observed in cosmopolitan D. melanogaster is due to a gl utamic acid substitution occurring in a phylogenetically conserved lys ine that has been identified as part of the ''hinged-lid'' active site of the enzyme. This observation suggests that the replacement polymor phism may have important functional consequences. One replacement poly morphism was also observed in D. simulans, although its functional rel evance is more difficult to assess, since it affects a site that is no t strongly conserved. This amino acid change in D. simulans is associa ted with a single lineage possessing seven unique silent substitutions , which may be indicative of balancing selection or population subdivi sion. The absence of fixed amino acid differences between D. melanogas ter and D. simulans and only a single difference with D. yakuba sugges ts that triose phosphate isomerase is under strong functional constrai nt. Silent variation is slightly higher for D. melanogaster than for D . simulans. Finally, we outline the general lack of evidence for old b alanced polymorphisms at allozyme loci in D. melanogaster.