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

View ORCID ProfileAdam D Hargreaves, Long Zhou, Josef Christensen, Ferdinand Marlétaz, 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
doi: https://doi.org/10.1101/093401
Adam D Hargreaves
1Department of Zoology, University of Oxford, Oxford, OX1 3PS, UK
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  • ORCID record for Adam D Hargreaves
Long Zhou
2China National Genebank, BGI-Shenzhen, 518083, Shenzhen, Guangdong, China
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Josef Christensen
3Novo Nordisk, Måløv, Denmark
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Ferdinand Marlétaz
1Department of Zoology, University of Oxford, Oxford, OX1 3PS, UK
4Molecular Genetics Unit, Okinawa Institute of Science and Technology Graduate University, Onna, Okinawa 904-0495, Japan.
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Shiping Liu
2China National Genebank, BGI-Shenzhen, 518083, Shenzhen, Guangdong, China
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Fang Li
2China National Genebank, BGI-Shenzhen, 518083, Shenzhen, Guangdong, China
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Peter Gildsig Jansen
3Novo Nordisk, Måløv, Denmark
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Enrico Spiga
5Francis Crick Institute, London, UK
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Matilde Thye Hansen
3Novo Nordisk, Måløv, Denmark
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Signe Vendelbo Horn Pedersen
3Novo Nordisk, Måløv, Denmark
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Shameek Biswas
6Novo Nordisk Research Centre, Seattle, USA
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Kyle Serikawa
6Novo Nordisk Research Centre, Seattle, USA
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Brian A Fox
6Novo Nordisk Research Centre, Seattle, USA
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William R Taylor
5Francis Crick Institute, London, UK
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John F Mulley
7School of Biological Sciences, Bangor University, UK
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Guojie Zhang
2China National Genebank, BGI-Shenzhen, 518083, Shenzhen, Guangdong, China
8State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, 650223, Kunming, China
9Centre for Social Evolution, Department of Biology, Universitetsparken 15, University of Copenhagen, DK-2100 Copenhagen, Denmark
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R Scott Heller
3Novo Nordisk, Måløv, Denmark
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Peter W H Holland
1Department of Zoology, University of Oxford, Oxford, OX1 3PS, UK
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Abstract

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.

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Posted December 17, 2016.
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Genome sequence of a diabetes-prone desert rodent reveals a mutation hotspot around the ParaHox gene cluster
Adam D Hargreaves, Long Zhou, Josef Christensen, Ferdinand Marlétaz, 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
bioRxiv 093401; doi: https://doi.org/10.1101/093401
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Genome sequence of a diabetes-prone desert rodent reveals a mutation hotspot around the ParaHox gene cluster
Adam D Hargreaves, Long Zhou, Josef Christensen, Ferdinand Marlétaz, 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
bioRxiv 093401; doi: https://doi.org/10.1101/093401

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