Distinct but parallel evolutionary patterns between alcohol and aldehyde dehydrogenases: addition of fish/human betaine aldehyde dehydrogenase divergence

Abstract

Alcohol dehydrogenases (ADHs) of the MDR type (medium-chain dehydrogenases/reductases) have diverged into two evolutionary groups in eukaryotes: a set of 'constant' enzymes (class III) typical of basal enzymes, and a set of 'variable' enzymes (remaining classes) suggesting 'evolving' forms. The variable set has larger overall variability, different segment variability, and variability also in functional segments. Using a major aldehyde dehydrogenase (ALDH) from cod liver and fish ALDHs deduced from the draft genome sequence of Fugu rubripes (Japanese puffer fish), we found that ALDHs form more complex patterns than the ADHs. Nevertheless, ALDHs also group into 'constant' and 'variable' sets, have separate segment variabilities, and distinct functions. Betaine ALDH (class 9 ALDH) is 'constant,' has three segments of variability, all non-functional, and a limited fish/human divergence, reminiscent of the ADH class III pattern. Enzymatic properties of fish betaine ALDH were also determined. Although all ALDH patterns are still not known, overall patterns are related to those of ADH, and group separations may be distinguished. The results can be interpreted functionally, support ALDH isozyme distinctions, and assign properties to the multiplicities of the ADH and ALDH enzymes.

Merging protein, gene and genomic data: the evolution of the MDR-ADH family

“…Later, in Takifugu rubripes (fugu), two forms were reported (Hjelmqvist et al, 2003), and as each clusters with one cod counterpart (Figure 4 and Supplementary information #2), we have named them H and L. Moreover, searches in EST and genomic databases have rendered ADH3L sequences in Tetraodon nigroviridis (pufferfish), and ADH3 H in Cyprinus carpio (carp), Danio rerio (zebrafish), Gasterosteus aculeatus (three-spined stickleback), Oryzias latipes (Japanese medaka) and Sparus aurata (sea bream) ( Table 1). Concerning ADH1 multiplicity, to the A forms initially reported in Gadus callarias (Baltic cod) (Danielsson et al, 1996), T. rubripes (Hjelmqvist et al, 2003) and D. rerio (ADH8) (Reimers et al, 2004), new sequences have now been added from genome searches: C. carpio, I. punctatus, O. mykiss, O. latipes. Also, after database searches, a new ADH1B subclass can be described in D. rerio, I. punctatus and T. rubripes (Table 1 and Figure 4).…”

Kinetic and structural analysis of human ALDH9A1

“…Second, the highly conserved glutamine Gln 161 in ALDH9A1 is substituted by the methionine Met 170 in GmALDH9A2. The cod enzyme, which has only been studied with six substrates [30], displays the highest catalytic efficiency for BAL followed by benzaldehyde. As no other aminoaldehydes including TMABAL were tested, it is difficult to deduce any effect of these two substitutions on substrate specificity.…”