Genome sequence of a diabetes-prone desert rodent reveals a mutation hotspot around the ParaHox gene cluster

The sand ratPsammomys obesusis 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 diabetes2which, in extreme cases, leads to pancreatic failure and death3,4. Previous studies have reported inability to detect thePdx1gene 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 elusivePdx1.The sequence ofPdx1has 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.