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Originally published as Genetics Published Articles Ahead of Print on February 1, 2008.
Genetics, Vol. 178, 1683-1691, March 2008, Copyright © 2008
doi:10.1534/genetics.108.087023
Adaptive Evolution of the Insulin Two-Gene System in Mouse
Meng-Shin Shiao*,
,1,
Ben-Yang Liao*,3,
Manyuan Long,2 and
Hon-Tsen Yu*,2,4
* Institute of Zoology and Department of Life Science, National Taiwan University, Taipei 106, Taiwan, Republic of China and Department of Ecology and Evolution, University of Chicago, Chicago, Illinois 60637
4 Corresponding author: Institute of Zoology and Department of Life Science, National Taiwan University, Taipei 106, Taiwan, Republic of China.
E-mail: ayu{at}ntu.edu.tw
Insulin genes in mouse and rat compose a two-gene system in which Ins1 was retroposed from the partially processed mRNA of Ins2. When Ins1 originated and how it was retained in genomes still remain interesting problems. In this study, we used genomic approaches to detect insulin gene copy number variation in rodent species and investigated evolutionary forces acting on both Ins1 and Ins2. We characterized the phylogenetic distribution of the new insulin gene (Ins1) by Southern analyses and confirmed by sequencing insulin genes in the rodent genomes. The results demonstrate that Ins1 originated right before the mouse–rat split (
20 MYA), and both Ins1 and Ins2 are under strong functional constraints in these murine species. Interestingly, by examining a range of nucleotide polymorphisms, we detected positive selection acting on both Ins2 and Ins1 gene regions in the Mus musculus domesticus populations. Furthermore, three amino acid sites were also identified as having evolved under positive selection in two insulin peptides: two are in the signal peptide and one is in the C-peptide. Our data suggest an adaptive divergence in the mouse insulin two-gene system, which may result from the response to environmental change caused by the rise of agricultural civilization, as proposed by the thrifty-genotype hypothesis.