Phylogeny of g6pc1 Genes and Their Functional Divergence among Sarcopterygian Vertebrates: Implications for Thermoregulatory Strategies.

ABSTRACT

Glucose-6-phosphatase catalytic subunit 1 (G6PC1) catalyzes the final rate-limiting step in endogenous glucose production and is critically important for glucose homeostasis. Although a single g6pc1 gene is present in mammals, other vertebrates possess two to five paralogs. Functional divergence between paralogs has been reported in actinopterygians and has been implicated in the acquisition of adaptive characteristics. Such reports make sarcopterygian g6pc1 an interesting research topic because unlike the aquatic habitat of actinopterygians, sarcopterygians have successfully adapted to terrestrial environments. However, little is known about the evolution of sarcopterygian g6pc1. In the present study, the evolutionary history of sarcopterygian g6pc1 was investigated using molecular phylogeny, synteny analyses, and comparison of the genomic environment. Functional divergence between paralogs was also investigated in a reptilian species, the Japanese gecko, with a focus on gene expression in the liver. Evolutionary analyses suggested that amphibians and amniotes acquired duplicated genes independently. Among the amniotes, gene duplication occurred at the root of the reptilian-avian lineage, giving rise to g6pc1-1 and g6pc1-2 classes. While the avian lineage subsequently lost the g6pc1-1, the reptiles retained both classes. This co-occurrence of gene loss and endothermy acquisition, together with the observation that mammals possess only a single gene, suggests that the duplicated g6pc1 is dispensable for endotherms. Quantitative RT-PCR analyses revealed that the two gecko genes respond differently to E2 administration, as the expression of g6pc1-1 was downregulated by E2, whereas g6pc1-2 showed no significant response. Such paralog-specific responses suggest functional divergence between paralogs, which is possibly related to reproduction.