PT - JOURNAL ARTICLE AU - Adam D Hargreaves AU - Long Zhou AU - Josef Christensen AU - Ferdinand Marlétaz AU - Shiping Liu AU - Fang Li AU - Peter Gildsig Jansen AU - Enrico Spiga AU - Matilde Thye Hansen AU - Signe Vendelbo Horn Pedersen AU - Shameek Biswas AU - Kyle Serikawa AU - Brian A Fox AU - William R Taylor AU - John F Mulley AU - Guojie Zhang AU - R Scott Heller AU - Peter W H Holland TI - Genome sequence of a diabetes-prone desert rodent reveals a mutation hotspot around the ParaHox gene cluster AID - 10.1101/093401 DP - 2016 Jan 01 TA - bioRxiv PG - 093401 4099 - http://biorxiv.org/content/early/2016/12/17/093401.short 4100 - http://biorxiv.org/content/early/2016/12/17/093401.full AB - The sand rat Psammomys obesus is a gerbil native to deserts of North Africa and the Middle East1. Sand rats survive with low caloric intake and when given high carbohydrate diets can become obese and develop type II diabetes2 which, in extreme cases, leads to pancreatic failure and death3,4. Previous studies have reported inability to detect the Pdx1 gene or protein in gerbils5–7, suggesting that absence of this key insulin-regulating homeobox gene might underlie diabetes susceptibility. Here we report sequencing of the sand rat genome and discovery of an extensive, mutationally-biased GC-rich genomic domain encompassing many essential genes, including the elusive Pdx1. The sequence of Pdx1 has been grossly affected by GC-biased mutation leading to the highest divergence observed in the animal kingdom. In addition to molecular insights into restricted caloric intake in a desert species, the discovery that specific chromosomal regions can be subject to elevated mutation rate has widespread significance to evolution.