On the Molecular Evolution of Leptin, Leptin Receptor, and Endospanin

Abstract

Over a decade passed between Friedman’s discovery of the mammalian leptin gene (1) and its cloning in fish (2) and amphibians (3). Since 2005, the concept of gene synteny conservation (vs. gene sequence homology) was instrumental in identifying leptin genes in dozens of species, and we now have leptin genes from all major classes of vertebrates. This database of LEP (leptin), LEPR (leptin receptor), and LEPROT (endospanin) genes has allowed protein structure modeling, stoichiometry predictions, and even functional predictions of leptin function for most vertebrate classes. Here, we apply functional genomics to model hundreds of LEP, LEPR, and LEPROT proteins from both vertebrates and invertebrates. We identify conserved structural motifs in each of the three leptin signaling proteins and demonstrate Drosophila Dome protein’s conservation with vertebrate leptin receptors. We model endospanin structure for the first time and identify endospanin paralogs in invertebrate genomes. Finally, we argue that leptin is not an adipostat in fishes and discuss emerging knockout models in fishes.

Adiposity signals predict vocal effort in Alston's singing mice

“…Among the many physiological measures of condition, leptin emerged as the most predictive of song effort, a pattern consistent with its signalling of fat stores [14]. Because leptin is a widely used hormone [56,58], it is likely to be useful measures of condition in a wide variety of species, and offers a logical focus for the study of the neural mechanisms governing display decisions. By expanding both the mechanistic depth of field studies and the taxonomic scope of physiological work, researchers may gain fundamental new insights into the mechanisms that underlie condition-dependent behaviours, and the processes by which they evolve.…”

Molecular cloning, characterization and evolutionary analysis of leptin gene in Chinese giant salamander, Andrias davidianus

“…Interestingly, leptins have been shown to be involved in early development [63] and innate immune previously [41], indicating that the multiple leptins in teleost are obtained through gene duplication that occurred in the ancestor of Cluopeocephala. Given the conserved tertiary structures from teleosts to mammals [2,34], the diverse physiological roles of leptins in different vertebrates characterized to date [74], and the common intracellular signaling pathways presented in all Tetrapoda as suggested by this research, the phylogenetic topology of vertebrate leptins obtained in this research suggest that it would be very interesting to detect whether there are different regulation mechanisms for pleiotropic roles or expressions of leptins throughout evolution.…”

Acyl-CoA-binding protein (ACBP): a phylogenetically conserved appetite stimulator

“…Irrespective of the aforementioned uncertainties, it appears clear that ACBP plays a major appetitestimulatory role throughout eukaryotic evolution, meaning that it triggers a range of different feeding behaviors in yeast (sporulation), nematodes (pharyngeal pumping), insects (mouth hook movement) and mammals (food intake). Since it operates independently from the leptin and ghrelin systems (which only exist in mammals) 35,36 , ACBP may indeed represent the phylogenetically most ancient "hunger factor". In a plausible scenario, starvation causes autophagy, resulting in the release of ACBP from cells, and ACBP then acts on cell surface receptors to stimulate feeding behaviors.…”