V. Hannaert et al., Comparison and evolutionary analysis of the glycosomal glyceraldehyde-3-phosphate dehydrogenase from different kinetoplastida, J MOL EVOL, 47(6), 1998, pp. 728-738
In this work, we present the sequences and a comparison of the glycosomal G
APDHs from a number of Kinetoplastida. The complete gene sequences have bee
n determined for some species (Crithidia fasciculata, Herpetomonas samuelpe
ssoai, Leptomonas seymouri, and Phytomonas sp), whereas for other species(p
anosoma brucei gambiense, Trypanosoma congolense, Trypanosoma vivax, and Le
ishmania major), only partial sequences have been obtained by PCR amplifica
tion The structure of all available glycosomal GAPDH genes was analyzed in
detail. Considerable variations were observed in both their nucleotide comp
osition and their codon usage. The GC content varies between 64.4% in L. se
ymouri and 49.5% in the previously sequenced GAPDH gene from Trypanoplasma
borreli. A highly biased codon usage was found in C. fasciculata, with only
34 triplets used, whereas in T. borreli 57 codons were employed. No obviou
s correlation could be observed between the codon usage and either the nucl
eotide composition or the level of gene expression. The glycosomal GAPDH is
a very well-conserved enzyme. The maximal overall difference observed in t
he amino acid sequences is only 25%. Specific insertions and extensions are
retained in all sequences. The residues involved in catalysis, substrate,
and inorganic phosphate binding are fully conserved, whereas some variabili
ty is observed in the cofactor-binding pocket. The implications of these da
ta for the design of new trypanocidal drugs targeted against GAPDH are disc
ussed. All available gene and amino acid sequences of glycosomal GAPDHs wer
e used for a phylogenetic analysis. The division of the Kinetoplastida into
two suborders, Bodonina and Trypanosomatina, was well supported, Within th
e letter group, the Trypanosoma species appeared to be monophyletic, wherea
s the other trypanosomatids form a second clade.