AMD and DDC are paralogues that arose as a result of a gene duplication, holding
structural and functional relationships. They code for two decarboxylases involved in
morphological differentiation, being essential for the sclerotization and melanization of
the newly moulted cuticle of Diptera. In addition, DDC is required for the production of
the neurotransmitters dopamine and serotonin (Wright 1996, and references therein).
DDC is conserved between Drosophila and humans and is expressed in the central nervous
system (CNS) as well as in the peripheral nervous system of insects and mammals (Wang
et al. 1996; Wright 1996). In D.melanogaster there are two isoforms of the enzyme, which
result from two alternative splicing path-ways in neural and epidermal tissue (O’Keefe et
al. 1995). The two genes combined have proven utility in determining previously
unresolved phylogenetic relationships between Drosophila subgenera and species
(Tatarenkov and Ayala 2001; Tatarenkov et al. 2001).
GPDH, the nicotinamide-adenine dinucleotide (NAD)-dependent cytoplasmic
glycerol-3-phosphate dehydrogenase, plays a crucial role in insect flight metabolism because
of its keystone position in the glycerophosphate cycle, which provides energy for flight in
the thoracic muscles of Drosophila (O’Brien and MacIntyre 1978). In Drosophila
melanogaster the Gpdh gene is located on chromosome 2 (O’Brien and MacIntyre 1972) and
consists of eight coding exons (Bewley et al. 1989; von Kalm et al. 1989). It produces
three isozymes by differential splicing of the last three exons (Cook et al. 1988). The
GPDH polypeptide can be divided into two main domains, the NAD-binding domain and
the catalytic domain. The NAD-binding domain (which in the rabbit is encompassed by
the first 118 amino acids) is more highly conserved than the catalytic domain (Bewley et
al. 1989). We have previously investigated the evolution of GPDH in Diptera
(Kwiatowski et al. 1997) and across the three multicellular kingdoms (Rodríguez-Trelles
et al. 2001a).
G6PD and PGD are prototype housekeeping enzymes, present in bacteria and all
eukaryotic cell types. They catalyse the first and the last steps in the pentose shunt.
Because the first step is rate limiting for the pathway, G6PD regulates the production of
NADPH, critical for lipid synthesis and detoxification, and ribose 5-phosphate required for
nucleotide and nucleic acid synthesis. The enzymes exhibit two domains for binding the
coenzyme and substrate. The G6pd locus is X-linked in D. melanogaster (denoted Zw gene)
and mammals. The active human G6PD exists in a dimer•tetramer equilibrium depending
on pH and ionic strength (reviewed in Shannon et al. 2000). Unlike other PGDs, the
enzyme of Schizosaccharomyces pombe is tetrameric (Tsai and Chen 1998). Deficiency of
G6PD and/or PGD causes chronic haemolytic anaemia, a common human enzymopathy.
The superoxide dismutases are abundant enzymes in aerobic organisms, with highly
specific superoxide dismutation activity that protects the cell against harm from free
oxygen radicals (Fridovich 1986). These enzymes have active centres that contain either
iron or manganese, or both copper and zinc (Fridovich 1986). The Cu Zn superoxide
dismutase (SOD) is a well-studied protein, found in eukaryotes but also in some bacteria
(Steinman 1988). The population genetics and evolution of SOD have been, for three
decades, the subject of numerous investigations in our laboratory (e.g. Ayala et al. 1971,
1974; Ayala 1972; Lee et al. 1981; Peng et al. 1986; Ayala 1997; Rodríguez-Trelles et al.
2001a).
10 FRANCISCO RODRÍGUEZ-TRELLES ET AL.