Institut de Biologie StructuraleGrenoble / France

Paleo biochemistry, a key to understanding the selection of enzyme properties

Studies providing insights into adaptative process of molecules to extreme conditions are of wide fundamental interest, as evolutionary processes impact the genomic organization, shape, function and phenotype of cells and their biomolecules. Thus evolutionary biochemistry allows to understand the fundamental process of exchange between the dynamic, structural and functional properties of enzymes.
In this work, scientists from the Institute of Structural Biology (IBS, Grenoble), in collaboration with the National Institute of Research in Digital Science and Technology (INRIA Rennes) and the Laboratory of Biometry and Evolutionary Biology (LBBE, Lyon), describe the evolutionary history (over a period of 500 million years) of malate dehydrogenases (MalDH) within Halobacteria, a metabolic enzyme facing extreme physicochemical conditions. They resurrected nine ancestors along the inferred halobacterial MalDH phylogeny and compared their biochemical properties with those of five modern halobacterial MalDHs. They found that a variety of evolutionary processes such as amino acid replacement, gene duplication, loss of MalDH gene and replacement owing to horizontal transfer resulted in significant differences in solubility, stability and catalytic. Unexpectedly, they analyzed that destabilizing mutations in a given circumstances could be at the origin of a gain of stability allowing a secondary adaptation in an environment with a very high pH. These researchers also showed the very important role of lateral gene transfer between species that allows a very rapid adaptive molecular response.
This work revealed that activity, stability and solubility of an enzyme are parameters that evolve independently of each other during an adaptive process.This is a fundamental finding that should be taken into account by researchers interested in protein engineering.

Resurrection of Ancestral Malate Dehydrogenases Reveals the Evolutionary History of Halobacterial Proteins : Deciphering gene trajectories and changes in biochemical properties. Samuel Blanquart, Mathieu Groussin, Aline Le Roy, Gergely J Szöllosi, Eric Girard, Bruno Franzetti, Manolo Gouy and Dominique Madern. Molecular Biology and Evolution, msab146,

Contact : Dominique Madern (IBS/Extremophiles and Large Molecular Assemblies Group)