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Proc Natl Acad Sci U S A. 2017 Jul 18;114(29):7677-7682. doi: 10.1073/pnas.1702930114. Epub 2017 Jul 3.

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

Author information

1
Department of Zoology, University of Oxford, Oxford, OX1 3PS, United Kingdom.
2
China National Genebank, BGI-Shenzhen, 518083, Shenzhen, Guangdong, China.
3
Novo Nordisk, Måløv, DK-2760, Denmark.
4
Molecular Genetics Unit, Okinawa Institute of Science and Technology Graduate University, Onna, Okinawa 904-0495, Japan.
5
Francis Crick Institute, London, NW1 1AT, United Kingdom.
6
Novo Nordisk Research Centre, Seattle, WA 98109.
7
School of Biological Sciences, Bangor University, Bangor, LL57 2DG, United Kingdom.
8
China National Genebank, BGI-Shenzhen, 518083, Shenzhen, Guangdong, China; peter.holland@zoo.ox.ac.uk zhanggj@genomics.cn richardscottheller@gmail.com.
9
State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, 650223, Kunming, China.
10
Centre for Social Evolution, Department of Biology, University of Copenhagen, DK-2100 Copenhagen, Denmark.
11
Novo Nordisk, Måløv, DK-2760, Denmark; peter.holland@zoo.ox.ac.uk zhanggj@genomics.cn richardscottheller@gmail.com.
12
Department of Zoology, University of Oxford, Oxford, OX1 3PS, United Kingdom; peter.holland@zoo.ox.ac.uk zhanggj@genomics.cn richardscottheller@gmail.com.

Abstract

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.

KEYWORDS:

Pdx1; desert rodent; gene conversion; homeobox; type 2 diabetes

PMID:
28674003
PMCID:
PMC5530673
DOI:
10.1073/pnas.1702930114
[Indexed for MEDLINE]
Free PMC Article

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