Genome sequence of a diabetes-prone rodent reveals a mutation hotspot around the ParaHox gene cluster.
Adam D HargreavesLong ZhouJosef ChristensenFerdinand MarletazShiping LiuFang LiPeter Gildsig JansenEnrico SpigaMatilde Thye HansenSigne Vendelbo Horn PedersenShameek BiswasKyle SerikawaBrian A FoxWilliam R TaylorJohn Frederick MulleyGuojie ZhangR Scott HellerPeter W H HollandPublished in: Proceedings of the National Academy of Sciences of the United States of America (2017)
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.
Keyphrases
- copy number
- genome wide
- type diabetes
- genome wide identification
- drinking water
- glycemic control
- oxidative stress
- small molecule
- dna methylation
- cardiovascular disease
- single cell
- weight loss
- high throughput
- metabolic syndrome
- weight gain
- gene expression
- cerebral ischemia
- physical activity
- gas chromatography
- brain injury