New insight into the classification and evolution of glucose transporters in the Metazoa

Abstract

Because glucose is an essential energy source for living organisms, glucose transporters (GLUTs) are present in all species worldwide. Encoded by the solute carrier family 2 gene family, the GLUT proteins generally have 12 transmembrane helices (TMHs). In total, 14 GLUT proteins have been identified in humans (hGLUTs), and they are divided into 3 classes on the basis of their transport characteristics and sequence similarities. Herein, we report the use of protein sequence similarity networks (SSNs) to visualize the sequence trends of 4101 GLUT proteins across the Metazoa. The SSNs separated the metazoan proteins into 3 new classes that were different from the traditional classification system. In the new system, 9 of the 14 hGLUTs (hGLUT1–5, 7, 9, 11, and 14) were grouped into class I, 3 (hGLUT10, 12, and 13) were grouped into class II, and 2 (hGLUT6 and 8) were grouped into class III, as also supported by the phylogenetic tree. Multiple sequence alignments further showed that the conserved residues in each class were different. Furthermore, the hGLUTs in each class showed unique evolutionary characteristics, with similar nonsynonymous‐to‐synonymous divergence ratios and similar regions under conservative selection pressure. Of note, GLUTs with 3, 6, 18, 24, and 36 TMHs were identified among the metazoan genomes, and 1 Chinese hamster protein with 6 TMHs showed GLUT activity. In summary, this large‐scale sequence analysis provided new insights into the classification and evolution of GLUTs and further showed that gene duplication and fusion could have been important drivers during the evolution of these transporter molecules.—Jia, B., Yuan, D. P., Lan, W. J., Xuan, Y. H., Jeon, C. O. New insight into the classification and evolution of glucose transporters in the Metazoa. FASEB J. 33, 7519–7528 (2019). http://www.fasebj.org

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“…Previous SSN studies of glycyl radical enzymes and transporters have suggested that proteins in each cluster of an SSN share a similar biochemical activity; 26,27 however, this conclusion does not seem to apply to BSH clusters. The enzymes in Cluster 2 have been well-studied.…”

“…Although the SSN methods are based on sequence identities from BLAST bit-scores, which is different from sequence alignments in phylogenetic analyses, previous studies have shown that SSNs serve as a visually useful tool to reveal sequence-structurefunction associations and evolutionary relationships between protein families. 25,26 In case of BSHs, previous studies have classified BSHs into three, four, or eight clusters based on phylogenetic analysis; however, these analyses were based on <400 protein sequences. [15][16][17] Song et al grouped BSHs into eight clusters using phylogenetic analysis, but the classification separated several BSHs with high sequence identity into different clusters, 17 which led to overclassification.…”

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