Fig. 5.

Physiological and genomic evidence showed vital function of SLC2A12 in wild songbirds. (A) Blood glucose levels are lower in highland songbirds in contrast to lowland birds (n = 8 for Pa. mo (L) and snowfinch, and 6 for Pa. mo (H)). (B, C) Highland birds increase glucose tolerance and insulin sensitivity. Two tailed t-test is used to perform significant analysis. *P value <0.05, **P value <0.01, and ***P value <0.0001. D) RNA-seq analysis identifies 407 DEGs shared by all highlanders, and these genes enrich in insulin resistance and insulin signaling pathway functions (n = 8 for Pa. mo (L), and 10 for highland birds). (E) Protein and gene abundance of SLC2A12 are overexpressed in highlander muscles (n = 8 for Pa. mo (L), and 10 for snowfinches and Pa. mo (H)). (F) Immunofluorescence staining shows more SLC2A12 translocated to the myolemma in highland birds. Green and blue indicate SLC2A12 protein and nuclei, respectively. (G) Genotypes of the lowlander and highlanders at SLC2A12 1703 SNP. The putatively advantageous homozygote is shown in black, and heterozygote was shown in gray. (H) SLC2A12-G alleles at site 1073 is associated with low blood glucose level in lowland populations (n = 4 each). (I) Modeling of the structural changes in SLC2A12 caused by the arginine–lysine dimorphism at residue 543 predicted a van der Waals interaction is formed between 543Lys and 254Ser. Latin name abbreviation is presented as follow. Pa. mo (L) for lowland tree sparrow (Passer montanus); Pa. mo (H) for highland tree sparrow (Passer montanus); Py. ru for rufous-necked snowfinch (Pyrgilauda ruficollis); On. ta for white-rumped snowfinch (Onychostruthus taczanowskii); Op. hoazin for hoatzin (Opisthocomus hoazin).