Evidence for Positive Selection on the Leptin Gene in Cetacea and Pinnipedia

Abstract

The leptin gene has received intensive attention and scientific investigation for its importance in energy homeostasis and reproductive regulation in mammals. Furthermore, study of the leptin gene is of crucial importance for public health, particularly for its role in obesity, as well as for other numerous physiological roles that it plays in mammals. In the present work, we report the identification of novel leptin genes in 4 species of Cetacea, and a comparison with 55 publicly available leptin sequences from mammalian genome assemblies and previous studies. Our study provides evidence for positive selection in the suborder Odontoceti (toothed whales) of the Cetacea and the family Phocidae (earless seals) of the Pinnipedia. We also detected positive selection in several leptin gene residues in these two lineages. To test whether leptin and its receptor evolved in a coordinated manner, we analyzed 24 leptin receptor gene (LPR) sequences from available mammalian genome assemblies and other published data. Unlike the case of leptin, our analyses did not find evidence of positive selection for LPR across the Cetacea and Pinnipedia lineages. In line with this, positively selected sites identified in the leptin genes of these two lineages were located outside of leptin receptor binding sites, which at least partially explains why co-evolution of leptin and its receptor was not observed in the present study. Our study provides interesting insights into current understanding of the evolution of mammalian leptin genes in response to selective pressures from life in an aquatic environment, and leads to a hypothesis that new tissue specificity or novel physiologic functions of leptin genes may have arisen in both odontocetes and phocids. Additional data from other species encompassing varying life histories and functional tests of the adaptive role of the amino acid changes identified in this study will help determine the factors that promote the adaptive evolution of the leptin genes in marine mammals.

Hormone and metabolite changes associated with extended breeding fasts in male northern elephant seals (Mirounga angustirostris)

“…The consistency in this uncoupling across multiple species may signify a common mechanism by which metabolic expenditure is controlled in species that incorporate fasting as part of their natural history. However, we also note there is evidence that fasting-adapted penguins lack leptin activity while maintaining the tissue receptor (Yosefi et al, 2010) and that the leptin gene is under positive selection in phocids (Yu et al, 2011), suggesting the potential for unique physiological roles in this taxa.…”

Natural selection and adaptive evolution of leptin

“…In humans, mutation of this gene results in a profound obesity and type II diabetes [12,[20][21][22][23]. Therefore, due to its critical role in obesity, the study of leptin will shed insight into molecular mechanism of energy homeostasis, future pharmaceutical intervention and public health [9,10,24].…”

“…The leptin gene, spanning over 4.5-kb, consists of three exons and two introns [9,25]. The coding exons (exons 2 and 3) are 501 bp in length in total.…”

“…The coding exons (exons 2 and 3) are 501 bp in length in total. Leptin contains an amino-terminal signal peptide (21 residues) and a mature peptide (146 residues), with four α-helices (helices A-D) and a distorted segment E in the CD loop [9,[26][27][28] (Figure 1).Generally, leptin appears to be highly conserved due to its functional importance [12,[29][30][31][32]. However, episodes of rapid sequence evolution and positive selection have been…”

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

“…The identity of the leptin protein in Xenopus to that of pufferfish, human, and tiger salamander (Ambystoma tigrinum) is 13%, 35%, and 60%, respectively [6,7,9]. Although, positive selections of leptins are revealed in several mammal lineages, for example, pikas (Ochotona curzoniae), Cetacea and Pinnipedia, and heterothermic bats [24][25][26], the conserved gene structure (three exons separated by two introns) and secondary and tertiary structures of leptins were found from teleosts to mammals [2,3,6,11,27,28]. Phylogeny reconstruction of vertebrate leptins showed that most vertebrates form distinct clades with topology consistent with the generally accepted vertebrate topology except that the relationships among teleosts remain inconsistent [2,11,29].…”