Abstract

SummaryThe feral pigs of Ossabaw Island (USA) have an outstanding propensity to obesity and develop complete metabolic syndrome (MetS) upon prolonged high energy dieting. We now report the first high quality genome of the Ossabaw pig with Contig N50 of ∼6.03 Mb, significantly higher than most other published pig genomes. Genomic comparison to Duroc reveals that variations including SNPs, INDELs and one ∼2 Mb inversion identified in Ossabaw pig may be related to its “thrifty” phenotype. Finally, an important positively selected gene (PSG) was found to be LEPR (leptin receptor) containing two positively selected sites which may lead to pseudogenization of this gene with possible significant effects on obesity and inflammation development. This work provides the first complete mapping of a genome representing a naturally ‘feast and famine’ evolved phenotype of MetS, serving as a blueprint to guide the search for new targets and new biomarkers for obesity comorbidities.

Highlights

  • Obesity is a major risk factor for globally prevalent serious diseases like cardiovascular diseases, type 2 diabetes, and cancer, which are leading causes of mortality worldwide (Bluher, 2019)

  • Genomic comparison to Duroc reveals that variations including single nucleotide polymorphisms (SNPs), INDELs and one 2 Mb inversion identified in Ossabaw pig may be related to its ‘‘thrifty’’ phenotype

  • An important positively selected gene (PSG) was found to be LEPR containing two positively selected sites which may lead to pseudogenization of this gene with possible significant effects on obesity and inflammation development

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Summary

Introduction

Obesity is a major risk factor for globally prevalent serious diseases like cardiovascular diseases, type 2 diabetes, and cancer, which are leading causes of mortality worldwide (Bluher, 2019). Animal models faithfully mimicking the complex human state of obesity are pivotal, i.e., human translational animal models in which a complete MetS and development of co-morbidities are obtained upon diet-induced obesity (Kleinert et al, 2018; Reilly and Saltiel, 2017) In this respect, the pig has emerged as highly promising (Bellinger et al, 2006; Kleinert et al, 2018; Spurlock and Gabler, 2008; Zhang and Lerman, 2016). The Ossabaw pig is a feral pig breed developed in isolation for approximately 500 years by natural evolution (Sturek et al, 2015) on Ossabaw Island (Georgia, USA), host to the only wild-living colony in the world They descend from pigs introduced by Spanish explorers around 1500 (Mayer and Brisbin, 1991). The Ossabaw phenotype results from a ‘thrifty genotype’ characterized by an increased ability to convert food into body fat (Lloyd et al, 2006; Neel, 1962), presumably developed as a result of natural selection driven by the ‘feast and famine’ ecology of its Ossabaw Island habitat with a high seasonal variation in food supply (Brisbin and Mayer, 2001)

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