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 <2000 years 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 Correspondence: Xiangjiang Zhan, Fax: +86 (0)1064807099; E-mail: zhanxj@ioz.ac.cn 1 These two authors contributed equally to the paper. highland adaptation involve relatively few genes, but are nonetheless more complex than previously thought and involve fine-tuned transcriptional responses and genomic adaptation.

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Flight loss in birds is as characteristic of the class Aves as flight itself. Although morphological and physiological differences are recognized in flight-degenerate bird species, their contributions to recurrent flight degeneration events across modern birds and underlying genetic mechanisms remain unclear. Here, in an analysis of 295 million nucleotides from 48 bird genomes, we identify two convergent sites causing amino acid changes in ATGL Ser321Gly and ACOT7 Ala197Val in flight-degenerate birds, which to our knowledge have not previously been implicated in loss of flight. Functional assays suggest that Ser321Gly reduces lipid hydrolytic ability of ATGL, and Ala197Val enhances acyl-CoA hydrolytic activity of ACOT7. Modeling simulations suggest a switch of main energy sources from lipids to carbohydrates in flight-degenerate birds. Our results thus suggest that physiological convergence plays an important role in flight degeneration, and anatomical convergence often invoked may not.