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

<jats:p>The sand rat<jats:italic>Psammomys obesus</jats:italic>is a gerbil native to deserts of North Africa and the Middle East<jats:sup>1</jats:sup>. Sand rats survive with low caloric intake and when given high carbohydrate diets can become obese and develop type II diabetes<jats:sup>2</jats:sup>which, in extreme cases, leads to pancreatic failure and death<jats:sup>3,4</jats:sup>. Previous studies have reported inability to detect the<jats:italic>Pdx1</jats:italic>gene or protein in gerbils<jats:sup>5–7</jats:sup>, 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<jats:italic>Pdx1.</jats:italic>The sequence of<jats:italic>Pdx1</jats:italic>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.</jats:p>