Overview of peroxisome proliferator-activated receptor gamma (PPARG) structure, DNA-binding specificity, and identification of human PPARG genetic variation conserved to fish. (A) Schematic illustrating the domain organization of human PPARG. (B) PPARG:RXRA-binding motifs for human (upper motif) and mouse (lower motif). Motifs are derived from the JASPAR database (http://jaspar.genereg.net/). (C) PPARG domain structure with dbSNPS predicted to be deleterious using SIFT and Polyphen, and conserved to zebrafish, Nile tilapia, and fugu. Red single nucleotide polymorphisms (SNPs) indicate functional verification (9). Yellow–brown histogram indicates the degree of conservation in PPARG between human, mouse, coelacanth, spotted gar, zebrafish, fugu, and Nile tilapia. Height and color indicate the degree of conservation.

Extensive shared synteny between mammals and fish at the Peroxisome proliferator-activated receptor (PPARG) locus. The predicted ancestral locus was inferred from comparing the loci documented in the figure, together with the chondrichthyan elephant shark (Callorhinchus milii) locus (not shown). The C. milii locus contained Cenp and Rab43 genes (indicated with an asterisk). Ts3R indicates the teleost-specific genome duplication. Note the inversion of TIMP4 and SYN2 upstream of PPARG in the mammalian lineage. Duplicated raf1 paralogs (raf1a and raf1b) are only retained in zebrafish and cavefish.

Acknowledgments
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