title: Origin and evolution of medium chain alcohol dehydrogenases.
abstract: Different lines of alcohol dehydrogenases (ADHs) have separate superfamily origins, already recognized but now extended and re-evaluated by re-screening of the latest databank update. The short-chain form (SDR) is still the superfamily with most abundant occurrence, most multiple divergence, most prokaryotic emphasis, and most non-complicated architecture. This pattern is compatible with an early appearance at the time of the emergence of prokaryotic cellular life. The medium-chain form (MDR) is also old but second in terms of all the parameters above, and therefore compatible with a second emergence. However, this step appears seemingly earlier than previously considered, and may indicate sub-stages of early emergences at the increased resolution available from the now greater number of data entries. The Zn-MDR origin constitutes a third stage, possibly compatible with the transition to oxidative conditions on earth. Within all these three lines, repeated enzymogeneses gave the present divergence. MDR-ADH origin(s), at a fourth stage, may also be further resolved in multiple or extended modes, but the classical liver MDR-ADH of the liver type can still be traced to a gene duplication ~550 MYA (million years ago), at the early vertebrate radiation, compatible with the post-eon-shift, "Cambrian explosion". Classes and isozymes correspond to subsequent and recent duplicatory events, respectively. They illustrate a peculiar pattern with functional and emerging evolutionary distinctions between parent and emerging lines, suggesting a parallelism between duplicatory and mutational events, now also visible at separate sub-stages. Combined, all forms show distinctive patterns at different levels and illustrate correlations with global events. They further show that simple molecular observations on patterns, multiplicities and occurrence give much information, suggesting common divergence rules not much disturbed by horizontal gene transfers after the initial origins.
authors.affiliation: Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden. Hans.Jornvall@ki.se
authors.forename: Hans
authors.initials: H
authors.lastname: Jörnvall
authors.forename: Joel
authors.initials: J
authors.lastname: Hedlund
authors.forename: Tomas
authors.initials: T
authors.lastname: Bergman
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Kallberg
authors.forename: Ella
authors.initials: E
authors.lastname: Cederlund
authors.forename: Bengt
authors.initials: B
authors.lastname: Persson
mesh_terms: D000426:Alcohol Dehydrogenase / Q000235:genetics*; D000818:Animals; D019143:Evolution, Molecular; D022761:Gene Transfer, Horizontal; D006801:Humans; D007527:Isoenzymes / Q000235:genetics; D008099:Liver / Q000201:enzymology / Q000378:metabolism; D010084:Oxidation-Reduction; D011387:Prokaryotic Cells / Q000201:enzymology / Q000378:metabolism
chemical_list: D007527:Isoenzymes; D000426:Alcohol Dehydrogenase