Natural Selection and Adaptive Evolution of Leptin in the Ochotona Family Driven by the Cold Environmental Stress

Abstract

BackgroundEnvironmental stress can accelerate the evolutionary rate of specific stress-response proteins and create new functions specialized for different environments, enhancing an organism's fitness to stressful environments. Pikas (order Lagomorpha), endemic, non-hibernating mammals in the modern Holarctic Region, live in cold regions at either high altitudes or high latitudes and have a maximum distribution of species diversification confined to the Qinghai-Tibet Plateau. Variations in energy metabolism are remarkable for them living in cold environments. Leptin, an adipocyte-derived hormone, plays important roles in energy homeostasis.Methodology/Principal FindingsTo examine the extent of leptin variations within the Ochotona family, we cloned the entire coding sequence of pika leptin from 6 species in two regions (Qinghai-Tibet Plateau and Inner Mongolia steppe in China) and the leptin sequences of plateau pikas (O. curzonia) from different altitudes on Qinghai-Tibet Plateau. We carried out both DNA and amino acid sequence analyses in molecular evolution and compared modeled spatial structures. Our results show that positive selection (PS) acts on pika leptin, while nine PS sites located within the functionally significant segment 85-119 of leptin and one unique motif appeared only in pika lineages-the ATP synthase α and β subunit signature site. To reveal the environmental factors affecting sequence evolution of pika leptin, relative rate test was performed in pikas from different altitudes. Stepwise multiple regression shows that temperature is significantly and negatively correlated with the rates of non-synonymous substitution (Ka) and amino acid substitution (Aa), whereas altitude does not significantly affect synonymous substitution (Ks), Ka and Aa.Conclusions/SignificanceOur findings support the viewpoint that adaptive evolution may occur in pika leptin, which may play important roles in pikas' ecological adaptation to extreme environmental stress. We speculate that cold, and probably not hypoxia, may be the primary environmental factor for driving adaptive evolution of pika leptin.

Mitochondrial phylogeography of the edible dormouse (Glis glis) in the western Palearctic region

“…However, the McDonald-Kreitman test showed no evidence of selection on the present Cytb gene of G. glis. It is possible that selection acted on another gene or genes more directly linked to hibernation or cold resistance, as was observed in Ochotona (Yang et al 2008). If so, this selection could have led to a European postglacial expansion from only a small number of cold-resistant animals, thereby resulting in the observed mitochondrial homogeneity.…”

VEGF189Expression Is Highly Related to Adaptation of the Plateau Pika (Ochotona curzoniae) Inhabiting High Altitudes

“…The plateau pika, as a typical plateau mammal, has been extensively studied to understand this adaptation. HIF-1a (Li et al, 2008, Zhao et al, 2004 and leptin (Yang et al, 2006) expression, and leptin (Yang et al, 2008) and Hb (Yingzhong et al, 2007) (n = 10). Asterisks indicate significant differences compared with the altitude of 3200 m (**p < 0.01, ***p < 0.001).…”

“…Zhou Le et al found that genetic distance and geographical distance of plateau pika population have no significant correlation (Zhou et al, 2007). Yang et al (2008) found that altitude has no significant effect on substitution rates of the gene-like leptin in pika. Here ten individuals of plateau pika from each site were used for mRNA analysis.…”

“…The molecular basis of these adaptations in the pika have occurred because of evolutionary changes in several critical factors, including HIF-1a (Li et al, 2008, Zhao et al, 2004, leptin (Yang et al, 2006(Yang et al, , 2008, and hemoglobin (Yingzhong et al, 2007). These factors have been reported to be expressed in a tissue-specific manner (Zhao et al, 2004) and with changes that are related to altitude (Li et al, 2008, Yang et al, 2006.…”

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].…”