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

By Adam D Hargreaves, Long Zhou, Josef Christensen, Ferdinand Marl├ętaz, Shiping Liu, Fang Li, Peter Gildsig Jansen, Enrico Spiga, Matilde Thye Hansen, Signe Vendelbo Horn Pedersen, Shameek Biswas, Kyle Serikawa, Brian A Fox, William R Taylor, John F. Mulley, Guojie Zhang, R Scott Heller, Peter W H Holland

Posted 17 Dec 2016
bioRxiv DOI: 10.1101/093401 (published DOI: 10.1073/pnas.1702930114)

The sand rat Psammomys obesus is a gerbil species native to deserts of North Africa and the Middle East. Sand rats survive with low caloric intake and when given high carbohydrate diets can become obese and develop symptoms of type II diabetes which, in extreme cases, leads to pancreatic failure and death. Previous studies have reported inability to detect the Pdx1 gene or protein in sand rats and other gerbils, leading to the hypothesis that absence of this insulin-regulating transcription factor may underlie diabetes susceptibility. Here we report sequencing of the sand rat genome and identification of an unusual, extensive and mutationally-biased GC-rich genomic domain encompassing many functionally essential genes, including the elusive Pdx1. The sequence of the Pdx1 homeobox gene has been grossly affected by extensive GC-biased mutation leading to the highest degree of divergence yet observed in the animal kingdom. In addition to molecular insights into restricted caloric intake in a desert species, the discovery of a chromosomal region subject to a greatly elevated mutation rate has widespread significance to evolution.

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