Mechanisms of dietary response in mice and primates: a role for EGR1 in regulating the reaction to human-specific nutritional content.

Kai Weng,Mehmet Somel,Augix Guohua Xu,Philipp Khaitovich,Haiyang Hu

doi:10.1371/journal.pone.0043915

Abstract

BackgroundHumans have a widely different diet from other primate species, and are dependent on its high nutritional content. The molecular mechanisms responsible for adaptation to the human diet are currently unknown. Here, we addressed this question by investigating whether the gene expression response observed in mice fed human and chimpanzee diets involves the same regulatory mechanisms as expression differences between humans and chimpanzees.ResultsUsing mouse and primate transcriptomic data, we identified the transcription factor EGR1 (early growth response 1) as a putative regulator of diet-related differential gene expression between human and chimpanzee livers. Specifically, we predict that EGR1 regulates the response to the high caloric content of human diets. However, we also show that close to 90% of the dietary response to the primate diet found in mice, is not observed in primates. This might be explained by changes in tissue-specific gene expression between taxa.ConclusionOur results suggest that the gene expression response to the nutritionally rich human diet is partially mediated by the transcription factor EGR1. While this EGR1-driven response is conserved between mice and primates, the bulk of the mouse response to human and chimpanzee dietary differences is not observed in primates. This result highlights the rapid evolution of diet-related expression regulation and underscores potential limitations of mouse models in dietary studies.

Highlights

Dietary change has been proposed as one of the main driving forces of human evolution, as well as one of the major causes of modern-day common metabolic disorders
Principal components analysis (PCA) of this combined dataset demonstrated a clear separation among samples according to their species identity (Figure 1A), indicating a large impact of species differences on total transcriptome variation
To test whether differences in transcription factors (TF) expression might be linked to gene expression differences between human and chimpanzee livers, we examined correlations between each TF’s expression and the expression of its predicted target genes

Summary

Introduction

Dietary change has been proposed as one of the main driving forces of human evolution, as well as one of the major causes of modern-day common metabolic disorders (reviewed in [1,2,3,4]). In the past several million years, the human diet has undergone several major shifts, including reliance on tubers, increased consumption of meat, the invention of food processing methods like cooking, and, more recently, a switch to high-calorie diets based on domesticated crops and animals. These changes may underlie multiple evolutionary adaptations [5]. The effects of dietary change in human evolution can be further detected among current-day populations with different traditional diets. We addressed this question by investigating whether the gene expression response observed in mice fed human and chimpanzee diets involves the same regulatory mechanisms as expression differences between humans and chimpanzees

Methods

Results

Conclusion