Genome sequence of a diabetes-prone 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 Frederick Mulley; Guojie Zhang; R. Scott Heller; Peter W. H. Holland

doi:10.1073/pnas.1702930114

Genome sequence of a diabetes-prone 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 Frederick Mulley, Guojie Zhang^*, R. Scott Heller, Peter W. H. Holland

^*Corresponding author for this work

Ecology and Evolution

18 Citations (Scopus)

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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.

Original language	English
Journal	Proceedings of the National Academy of Sciences of the United States of America
Volume	114
Issue number	29
Pages (from-to)	7677-7682
Number of pages	6
ISSN	0027-8424
DOIs	https://doi.org/10.1073/pnas.1702930114
Publication status	Published - 18 Jul 2017

Keywords

Desert rodent
Gene conversion
Homeobox
Pdx1
Type 2 diabetes

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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Hargreaves, A. D., Zhou, L., Christensen, J., Marlétaz, F., Liu, S., Li, F., Jansen, P. G., Spiga, E., Hansen, M. T., Pedersen, S. V. H., Biswas, S., Serikawa, K., Fox, B. A., Taylor, W. R., Mulley, J. F., Zhang, G., Heller, R. S., & Holland, P. W. H. (2017). Genome sequence of a diabetes-prone rodent reveals a mutation hotspot around the ParaHox gene cluster. Proceedings of the National Academy of Sciences of the United States of America, 114(29), 7677-7682. https://doi.org/10.1073/pnas.1702930114

Genome sequence of a diabetes-prone rodent reveals a mutation hotspot around the ParaHox gene cluster. / Hargreaves, Adam D.; Zhou, Long; Christensen, Josef et al.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 114, No. 29, 18.07.2017, p. 7677-7682.

Research output: Contribution to journal › Journal article › Research › peer-review

Hargreaves, AD, Zhou, L, Christensen, J, Marlétaz, F, Liu, S, Li, F, Jansen, PG, Spiga, E, Hansen, MT, Pedersen, SVH, Biswas, S, Serikawa, K, Fox, BA, Taylor, WR, Mulley, JF, Zhang, G, Heller, RS & Holland, PWH 2017, 'Genome sequence of a diabetes-prone rodent reveals a mutation hotspot around the ParaHox gene cluster', Proceedings of the National Academy of Sciences of the United States of America, vol. 114, no. 29, pp. 7677-7682. https://doi.org/10.1073/pnas.1702930114

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AU - Biswas, Shameek

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AU - Fox, Brian A.

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

Abstract

Keywords

UN SDGs

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