Skip to main content

Thank you for visiting You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Subspecific origin and haplotype diversity in the laboratory mouse



Here we provide a genome-wide, high-resolution map of the phylogenetic origin of the genome of most extant laboratory mouse inbred strains. Our analysis is based on the genotypes of wild-caught mice from three subspecies of Mus musculus. We show that classical laboratory strains are derived from a few fancy mice with limited haplotype diversity. Their genomes are overwhelmingly Mus musculus domesticus in origin, and the remainder is mostly of Japanese origin. We generated genome-wide haplotype maps based on identity by descent from fancy mice and show that classical inbred strains have limited and non-randomly distributed genetic diversity. In contrast, wild-derived laboratory strains represent a broad sampling of diversity within M. musculus. Intersubspecific introgression is pervasive in these strains, and contamination by laboratory stocks has played a role in this process. The subspecific origin, haplotype diversity and identity by descent maps can be visualized using the Mouse Phylogeny Viewer (see URLs).

This is a preview of subscription content, access via your institution

Relevant articles

Open Access articles citing this article.

Access options

Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.

Figure 1: Overall contribution of each subspecies to the genome of wild and laboratory mice.
Figure 2: Subspecific origin and haplotype diversity of chromosomes 6 and X.
Figure 3: Intersubspecific introgression and contamination by classical strains in the wild-derived inbred strains.
Figure 4: Identification of donor strains.


  1. Boursot, P., Auffray, J.C., Britton-Davidian, J. & Bonhomme, F. The evolution of the house mice. Annu. Rev. Ecol. Syst. 24, 119–152 (1993).

    Article  Google Scholar 

  2. Geraldes, A. et al. Inferring the history of speciation in house mice from autosomal, X-linked, Y-linked and mitochondrial genes. Mol. Ecol. 17, 5349–5363 (2008).

    Article  Google Scholar 

  3. Teeter, K.C. et al. Genome-wide patterns of gene flow across a house mouse hybrid zone. Genome Res. 18, 67–76 (2008).

    Article  CAS  Google Scholar 

  4. Yonekawa, H., Takahama, S., Gotoh, O., Miyashita, N. & Moriwaki, K. Genetic diversity and geographic distribution of Mus musculus subspecies based on the polymorphism of mitochondrial DNA. in Genetics in Wild Mice. Its application to Biomedical Research (eds Moriwaki, K., Shiroishi, T. and Yonekawa, H.) 25–40 (Japan Scientific Societies Press, Tokyo, Japan, 1994).

  5. Beck, J.A. et al. Genealogies of mouse inbred strains. Nat. Genet. 24, 23–25 (2000).

    Article  CAS  Google Scholar 

  6. Frazer, K.A. et al. A sequence-based variation map of 8.27 million SNPs in inbred mouse strains. Nature 448, 1050–1053 (2007).

    Article  CAS  Google Scholar 

  7. Yang, H., Bell, T.A., Churchill, G.A. & Pardo-Manuel de Villena, F . On the subspecific origin of the laboratory mouse. Nat. Genet. 39, 1100–1107 (2007).

    Article  CAS  Google Scholar 

  8. Guénet, J.L. & Bonhomme, F. Wild mice: an ever-increasing contribution to a popular mammalian model. Trends Genet. 19, 24–31 (2003).

    Article  Google Scholar 

  9. Mouse Genome Sequencing Consortium et al. Initial sequencing and comparative analysis of the mouse genome. Nature 420, 520–562 (2002).

  10. Sudbery, I. et al. Deep short-read sequencing of chromosome 17 from the mouse strains A/J and CAST/Ei identifies significant germline variation and candidate genes that regulate liver triglyceride levels. Genome Biol. 10, R112 (2009).

    Article  Google Scholar 

  11. Chesler, E.J. et al. The Collaborative Cross at Oak Ridge National Laboratory: developing a powerful resource for systems genetics. Mamm. Genome 19, 382–389 (2008).

    Article  Google Scholar 

  12. Guan, C., Ye, C., Yang, X. & Gao, J. A review of current large-scale mouse knockout efforts. Genesis 48, 73–85 (2010).

    CAS  PubMed  Google Scholar 

  13. Szatkiewicz, J.P. et al. An imputed genotype resource for the laboratory mouse. Mamm. Genome 19, 199–208 (2008).

    Article  Google Scholar 

  14. Harr, B. Genomic islands of differentiation between house mouse subspecies. Genome Res. 16, 730–737 (2006).

    Article  CAS  Google Scholar 

  15. Boursot, P. & Belkhir, K. Mouse SNPs for evolutionary biology: beware of ascertainment biases. Genome Res. 16, 1191–1192 (2006).

    Article  CAS  Google Scholar 

  16. White, M.A., Ané, C., Dewey, C.N., Larget, B.R. & Payseur, B.A. Fine-scale phylogenetic discordance across the house mouse genome. PLoS Genet. 5, e1000729 (2009).

    Article  Google Scholar 

  17. Yang, H. et al. A customized and versatile high-density genotyping array for the mouse. Nat. Methods 6, 663–666 (2009).

    Article  CAS  Google Scholar 

  18. Nagamine, C.M. et al. The musculus-type Y chromosome of the laboratory mouse is of Asian origin. Mamm. Genome 3, 84–91 (1992).

    Article  CAS  Google Scholar 

  19. Tucker, P.K., Lee, B.K., Lundrigan, B.L. & Eicher, E.M. Geographic origin of the Y chromosomes in “old” inbred strains of mice. Mamm. Genome 3, 254–261 (1992).

    Article  CAS  Google Scholar 

  20. Mihola, O., Trachtulec, Z., Vlcek, C., Schimenti, J.C. & Forejt, J. A mouse speciation gene encodes a meiotic histone H3 methyltransferase. Science 323, 373–375 (2009).

    Article  CAS  Google Scholar 

  21. Ideraabdullah, F.Y. et al. Genetic and haplotype diversity among wild-derived mouse inbred strains. Genome Res. 14, 1880–1887 (2004).

    Article  CAS  Google Scholar 

  22. Wang, J., Moore, K.J., Zhang, Q., Pardo-Manuel de Villena, F., Wang, W. & McMillan, L. Genome-wide compatible SNP intervals and their properties. Proceedings of ACM International Conference on Bioinformatics and Computational Biology (Niagara Falls, New York, USA, 2010).

Download references


This work was supported by the National Institute of General Medical Sciences (NIGMS) Centers of Excellence in Systems Biology program, grant GM-076468, by a US National Institutes of Health (NIH) grant to M.W.N. (R01 GM74245), by a grant to F.B. (ISEM 2010-141) and by a Czech Science Foundation grant to J.P. (206-08-0640). J.P.D. was partially supported by NIH Training Grant Number GM067553-04, University of North Carolina (UNC) Bioinformatics and Computational Biology Training Grant. J.P.D., R.J.B. and T.A.B. are partially supported by an NIH grant to F.P.-M.d.V. (P50 MH090338). We also thank F. Oyola for help annotating the samples genotyped in this study.

Author information

Authors and Affiliations



F.P.-M.d.V., G.A.C. and H.Y. conceived the study design and wrote the paper. H.Y., J.R.W., J.P.D., L.M. and C.E.W. carried out the bioinformatics analyses. J.P.D., T.A.B. and R.J.B. prepared the samples and conducted the targeted PCR amplification and sequencing. F.B., P.B., A.H.-T.Y., M.W.N., J.P. and P.T. provided biological samples. All authors contributed to the interpretation of the results and the writing of the manuscript.

Corresponding authors

Correspondence to Gary A Churchill or Fernando Pardo-Manuel de Villena.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Supplementary information

Supplementary Text and Figures

Supplementary Figures 1–10 and Supplementary Tables 2–6. (PDF 7417 kb)

Supplementary Table 1

Sample summary (XLSX 90 kb)

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Yang, H., Wang, J., Didion, J. et al. Subspecific origin and haplotype diversity in the laboratory mouse. Nat Genet 43, 648–655 (2011).

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI:

This article is cited by


Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing