High sequence identity does not mean redundancy of function: the case of plant malic enzymes

DRINCOVICH, M. F.

Congreso; Congreso Sociedad Española de Investigación en Bioquímica y Biología Molecular; 2019

The presence of multigenic families is a feature of eukaryotic genomes. High sequence homology among the members of multigenic families, or little phenotypic effects when an individual gene in such families is disrupted, is often attributed to gene redundancy. I will focus on the results we have obtained when studying the different family members of the malic enzyme (ME) from several plant species, which indicate that the different members of this family are not simply functionally redundant copies of one another. ME catalyses the oxidative decarboxylation of malate producing pyruvate, carbon dioxide and a reduced cofactor NAD(P)H, being involved in different metabolic pathways in several organisms due to the relevant physiological functions of the substrates and products of its reaction. In plants, it is one of the most important proteins that were recruited to fulfil key roles in C4 photosynthesis. The advances in genomics allowed us to perform the characterization of the complete set of MEs from different C3 and C4 plant species. Although the high degree of identity among the different ME members (more than 90% in some cases), we found that each isozyme plays specific roles in vivo with no overlapping functions with the other members. In this sense, we found that simple point mutations produced drastic modifications in the kinetic performance and/or regulation of each ME, identifying particlar molecular adaptations of each ME to fulfil particular physiological roles. Besides, the overexpression of different MEs in particular subcellular plant compartments rendered opposite phenotypes. As a whole, I will conclude that the notion of the biological function of a specific protein is a rather complex definition that refers to many levels of complexity in living organisms, and therefore can only be defined using a variety of complementary experimental approaches and skills