Phosphoenolpyruvate carboxykinase 1 gene (Pck1) displays parallel evolution between Old World and New World fruit bats.

Lei Zhu,Qiuyuan Yin,Shuyi Zhang,David M Irwin,Marc Robinson-Rechavi

doi:10.1371/journal.pone.0118666

Abstract

Bats are an ideal mammalian group for exploring adaptations to fasting due to their large variety of diets and because fasting is a regular part of their life cycle. Mammals fed on a carbohydrate-rich diet experience a rapid decrease in blood glucose levels during a fast, thus, the development of mechanisms to resist the consequences of regular fasts, experienced on a daily basis, must have been crucial in the evolution of frugivorous bats. Phosphoenolpyruvate carboxykinase 1 (PEPCK1, encoded by the Pck1 gene) is the rate-limiting enzyme in gluconeogenesis and is largely responsible for the maintenance of glucose homeostasis during fasting in fruit-eating bats. To test whether Pck1 has experienced adaptive evolution in frugivorous bats, we obtained Pck1 coding sequence from 20 species of bats, including five Old World fruit bats (OWFBs) (Pteropodidae) and two New World fruit bats (NWFBs) (Phyllostomidae). Our molecular evolutionary analyses of these sequences revealed that Pck1 was under purifying selection in both Old World and New World fruit bats with no evidence of positive selection detected in either ancestral branch leading to fruit bats. Interestingly, however, six specific amino acid substitutions were detected on the ancestral lineage of OWFBs. In addition, we found considerable evidence for parallel evolution, at the amino acid level, between the PEPCK1 sequences of Old World fruit bats and New World fruit bats. Test for parallel evolution showed that four parallel substitutions (Q276R, R503H, I558V and Q593R) were driven by natural selection. Our study provides evidence that Pck1 underwent parallel evolution between Old World and New World fruit bats, two lineages of mammals that feed on a carbohydrate-rich diet and experience regular periods of fasting as part of their life cycle.

Highlights

Food limitation is a common physiological challenge faced by animals and leads to a risk of death due to starvation
We examined the molecular evolution of the Pck1 gene, which plays an important role in the maintenance of glucose homeostasis during fasting in frugivirous bats, which eat carbohydrate-rich diets
By comparing Pck1 sequences among frugivorous and insectivorous bats, and other mammals, we provide the first data on the molecular evolution of this gene in frugivorous bats

Summary

Introduction

Food limitation is a common physiological challenge faced by animals and leads to a risk of death due to starvation. We focused on the molecular evolution of a gene involved in the resistance to the consequences of fasting. Maintaining glucose homeostasis under fasting conditions is essential [3], and many tissues are known to be involved in the regulation of blood glucose levels [4]. The liver plays a major role, as hepatic gluconeogenesis is the primary metabolic mechanism in the fasting state, in generating fuel to maintain the basic functions of other tissues, including skeletal muscle, red blood cells, and the brain [5]. The enzyme phosphoenolpyruvate carboxykinase (PEPCK), which catalyzes an irreversible reaction, is the rate-limiting step in gluconeogenesis [9]. Studies in Pck1knockout mice confirmed the importance of Pck in hepatic gluconeogenesis and glucose homeostasis, as Pck1-/- mice display severe hypoglycemia [14]. The level of transcription of PEPCK1 determines the rate of gluconeogenesis [15]

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