AMP kinase gene mutation is consistent with a thrifty phenotype (metabolic syndrome) in a population of feral swine

Abstract

The genetically obese Ossabaw Island feral pig (OIP) has a “thrifty” phenotype and is an excellent model for studying the metabolic syndrome. Sequencing of the hypervariable D-loop of mtDNA (with the cytochrome B gene) of 6 OIP’s revealed an Asian mtDNA sequence in all individuals. This haplotype was similar to that of pigs from the Canary Islands, which are known to have been the source of most pigs brought to the New World by Spanish explorers of the late 1500s. Examination of genes related to the obese OIP phenotype revealed 5/6 pigs to be homozygous for a Val199→Ile mutation (“IR”) in the PRKAG3 gene (the γ 3 isoform of AMP-activated protein kinase). The sixth animal was heterozygous for IR and the wt allele (“VR”). The IR allele is associated with low muscle glycogen and increased intramuscular fat, consistent with the obese OIP phenotype. In the mid-1970’s a Hampshire boar was introduced to Ossabaw I., and persistence of the belted coat color phenotype attests to its continuing genetic impact. However the “VQ” mutation (Arg200→Gln), which is associated with high muscle glycogen and low intramuscular fat (and is found in high frequency in Hampshires) was not found in any of the OIP sampled. This finding suggests selection for the IR mutation as a result of an unpredictable food supply. Leanness in pigs has been traced to an intron 3 mutation in the IGF2 gene. All 6 OIPs were homozygous for the wild type allele at this locus, as expected. These studies provide novel insights into the historical origins and selection for a “thrifty” phenotype in this unique population of feral swine. Support: HL62552, RR13223, ADA (MS), US DOE DE-FRC09-96SR18546 (ILB).