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 af dette arbejde

Ecology and Evolution

18 Citationer (Scopus)

123 Downloads (Pure)

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.

Originalsprog	Engelsk
Tidsskrift	Proceedings of the National Academy of Sciences of the United States of America
Vol/bind	114
Udgave nummer	29
Sider (fra-til)	7677-7682
Antal sider	6
ISSN	0027-8424
DOI	https://doi.org/10.1073/pnas.1702930114
Status	Udgivet - 18 jul. 2017

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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.
I: Proceedings of the National Academy of Sciences of the United States of America, Bind 114, Nr. 29, 18.07.2017, s. 7677-7682.

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › 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, bind 114, nr. 29, s. 7677-7682. https://doi.org/10.1073/pnas.1702930114

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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.",

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AU - Biswas, Shameek

AU - Serikawa, Kyle

AU - Fox, Brian A.

AU - Taylor, William R.

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AU - Heller, R. Scott

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AB - 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 rodent reveals a mutation hotspot around the ParaHox gene cluster

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