EPA-0580 – Examining the Genomic Architecture of Neuronal Glucose Transporter 3 from an Evolutionary Perspective

Abstract

Neuronal glucose transporter 3 (Glut3, SLC2A3) is essential in providing energy supply for neurons. Using mice as disease-models homozygous slc2a3 knock-out was found to be lethal in early embryonic phase while heterozygous form was associated to autism spectrum disorders.

The genomic region where SLC2A3 is located (12p13.3) is investigated intensely since NANOG – a homeobox gene critical in embryogenesis – and one of its impressive number of pseudogenes are also located here. Interestingly, this region also codes the gene SLC2A14 which is selectively expressed in testis and lung but shows 95% homology with SLC2A3. A tandem duplication event involving NANOG and SLC2A3 was proposed as a possible explanation to the current genomic architecture.

Since SLC2A3 was associated to a number of mental disorders this study aimed to examine SLC2A3 and the related region in an evolutionary perspective. Ensembl BLAST search and multi-species alignment were used to provide a comparison.

Our results support the notion that the region of 12p13.3 underwent a tandem duplication event which gave rise to new paralogues of NANOG and SLC2A3. Out of these SLC2A3 and SLC2A14 both remained functional. We argue that the region can be still a genomic spot susceptible to further rearrangements.