Evolutionary ancestry and novel functions of the mammalian glucose transporter (GLUT) family

We took a comparative genomic approach and have performed the first comprehensive and statistically supported phylogenetic analysis of all mammalian glucose transporter (GLUT) isoforms. Our data reveals the mammalian GLUT proteins segregate into five distinct classes. This evolutionary ancestry gives insight to structure, function and transport mechanisms within the groups. Combined with biological assays, we present novel evidence that, in response to changing nutrient availability and environmental pH, proton-coupled, active glucose symport function is maintained in mammalian cells.The analyses show the ancestry, evolutionary conservation and biological importance of the GLUT classes. These findings significantly extend our understanding of the evolution of mammalian glucose transport systems. They also reveal that mammals may have conserved an adaptive response to nutrient demand that would have important physiological implications to cell survival and growth.Sugars provide energy and structural components to all living cells. Due to their hydrophilic nature, sugars/polyols must first traverse biological lipid bi-layer membranes via carrier-mediated transport mechanisms. Transporter proteins are classified based on phylogenetic and functional data. Within the major facilitator (MF) superfamily the largest group is the sugar porter family [1]. Sugar porters are found in bacteria, archaea and eukarya and function by uniport or proton-coupled symport modes of transport [2]. Uniport, or facilitative sugar carriers, transport a substrate along its concentration gradient, thus transport is dependent upon extracellular nutrient levels. Symporters, or secondary-active transporters, can move a specific nutrient substrate against its concentration gradient in an energy requiring transport process. Energy is sourced from an electrochemical gradient coupling movement of nutrient substrate to translocation of ions.Bacteria often grow in conditions of extreme environmental flu