Population transcriptomes reveal synergistic responses of DNA polymorphism and RNA expression to extreme environments on the Qinghai-Tibetan Plateau in a predatory bird.

Shengkai Pan,Zhongru Gu,Li Hu,Shanshan Dong,Tongzuo Zhang,Qi Wu,Lucia Deutschova,Michael W Bruford,Zhenzhen Lin,Qiong Liu,Xinhai Li,Andrew Dixon,Xiangjiang Zhan,Zhengqin Rong

doi:10.1111/mec.14090

Abstract

Low oxygen and temperature pose key physiological challenges for endotherms living on the Qinghai-Tibetan Plateau (QTP). Molecular adaptations to high-altitude living have been detected in the genomes of Tibetans, their domesticated animals and a few wild species, but the contribution of transcriptional variation to altitudinal adaptation remains to be determined. Here we studied a top QTP predator, the saker falcon, and analysed how the transcriptome has become modified to cope with the stresses of hypoxia and hypothermia. Using a hierarchical design to study saker populations inhabiting grassland, steppe/desert and highland across Eurasia, we found that the QTP population is already distinct despite having colonized the Plateau <2000years ago. Selection signals are limited at the cDNA level, but of only seventeen genes identified, three function in hypoxia and four in immune response. Our results show a significant role for RNA transcription: 50% of upregulated transcription factors were related to hypoxia responses, differentiated modules were significantly enriched for oxygen transport, and importantly, divergent EPAS1 functional variants with a refined co-expression network were identified. Conservative gene expression and relaxed immune gene variation may further reflect adaptation to hypothermia. Our results exemplify synergistic responses between DNA polymorphism and RNA expression diversity in coping with common stresses, underpinning the successful rapid colonization of a top predator onto the QTP. Importantly, molecular mechanisms underpinning highland adaptation involve relatively few genes, but are nonetheless more complex than previously thought and involve fine-tuned transcriptional responses and genomic adaptation.

Highlights

Known as the ‘roof of the world’ and the ‘third pole’, the Qinghai–Tibetan Plateau covers a vast area of c. 2.5 million km2 featuring extreme altitude (>4000 m on average)
The hypoxia-inducible factor pathway, including the EPAS1 gene, has been identified as a major candidate for altitudinal adaptation in humans and other Qinghai–Tibetan Plateau (QTP) mammals (e.g. Yi et al 2010), and it is thought that they may mechanistically contribute to the constrained erythropoietic response in Tibetans (Cheviron & Brumfield 2011)
Several interspecific comparative genomic studies have identified candidate genes involved in temperature adaptation in QTP specialists such as sand lizards (Yang et al 2015) and ground tits (Qu et al 2013), and suggested that strong selection on lipid metabolism may have developed as an optimal energy conservation strategy to cope with the challenge for chronic cold stress

Summary

Introduction

Known as the ‘roof of the world’ and the ‘third pole’, the Qinghai–Tibetan Plateau covers a vast area of c. 2.5 million km featuring extreme altitude (>4000 m on average). Previous physiological studies have indicated that long-term exposure to hypoxia, possibly together with strong ultraviolet radiation, suppresses immune response in humans living in high-altitude environments (Facco et al 2005; Sica et al 2011). This phenomenon, has rarely been studied in genomic adaptation to the QTP except that a clear gene family contraction was observed in the immune-related genes in the ground tit genome, including the major histocompatibility complex (MHC) protein complex (Qu et al 2013). These studies have most focused on genomic sequence changes, and until now the contribution of gene expression to QTP adaptation is largely unknown

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Discussion

Conclusion