The Interaction of Natural Selection and GC Skew May Drive the Fast Evolution of a Sand Rat Homeobox Gene

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.

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

10.1101/093401 ◽

2016 ◽

Cited By ~ 1

Author(s):

Adam D Hargreaves ◽

Long Zhou ◽

Josef Christensen ◽

Ferdinand Marlétaz ◽

Shiping Liu ◽

...

Keyword(s):

North Africa ◽

Type Ii Diabetes ◽

Caloric Intake ◽

Homeobox Gene ◽

Sand Rat ◽

Diabetes Susceptibility ◽

Parahox Gene ◽

Desert Rodent ◽

Develop Type ◽

Rat Genome

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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