The sand rat Psammomys obesus is a gerbil species native to deserts of North Africa and the Middle East, and is constrained in its ecology because high carbohydrate diets induce obesity and type II diabetes that, in extreme cases, can lead to pancreatic failure and death. We report the sequencing of the sand rat genome and discovery of an unusual, extensive, and mutationally biased GC-rich genomic domain. This highly divergent genomic region encompasses several functionally essential genes, and spans the ParaHox cluster which includes the insulin-regulating homeobox gene Pdx1. The sequence of sand rat Pdx1 has been grossly affected by GC-biased mutation, leading to the highest divergence observed for this gene across the Bilateria. In addition to genomic insights into restricted caloric intake in a desert species, the discovery of a localized chromosomal region subject to elevated mutation suggests that mutational heterogeneity within genomes could influence the course of evolution.
The sand rat Psammomys obesus is a gerbil native to deserts of North Africa and the Middle East 1 . 22Sand rats survive with low caloric intake and when given high carbohydrate diets can become obese 23 and develop type II diabetes 2 which, in extreme cases, leads to pancreatic failure and death 3,4 . 24Previous studies have reported inability to detect the Pdx1 gene or protein in gerbils 5-7 , suggesting 25 that absence of this key insulin-regulating homeobox gene might underlie diabetes susceptibility. 26Here we report sequencing of the sand rat genome and discovery of an extensive, mutationally-27 biased GC-rich genomic domain encompassing many essential genes, including the elusive Pdx1. The 28 sequence of Pdx1 has been grossly affected by GC-biased mutation leading to the highest divergence 29 observed in the animal kingdom. In addition to molecular insights into restricted caloric intake in a 30 desert species, the discovery that specific chromosomal regions can be subject to elevated mutation 31 rate has widespread significance to evolution. 32Linking molecular change to phenotypic change is a central goal of evolutionary biology. Adaptation to 33 arid environments is particularly interesting because of the extreme physiological demands imposed by 34 low food and water availability. The sand rat Psammomys obesus (Fig. 1a) is a member of the subfamily 35Gerbillinae, most species of which live in deserts and arid environments (Fig. 1b). P. obesus has emerged 36 as a model for research into diet-induced type II diabetes because, if provided with high carbohydrate 37diets, the majority of individuals become obese and develop classic diabetes symptoms, in the most 38 extreme cases leading to pancreatic failure and death 2,3 . 39
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