On the subspecific origin of the laboratory mouse

Abstract

The genome of the laboratory mouse is thought to be a mosaic of regions with distinct subspecific origins. We have developed a high-resolution map of the origin of the laboratory mouse by generating 25,400 phylogenetic trees at 100-kb intervals spanning the genome. On average, 92% of the genome is of Mus musculus domesticus origin, and the distribution of diversity is markedly nonrandom among the chromosomes. There are large regions of extremely low diversity, which represent blind spots for studies of natural variation and complex traits, and hot spots of diversity. In contrast with the mosaic model, we found that most of the genome has intermediate levels of variation of intrasubspecific origin. Finally, mouse strains derived from the wild that are supposed to represent different mouse subspecies show substantial intersubspecific introgression, which has strong implications for evolutionary studies that assume these are pure representatives of a given subspecies.

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Figure 1: Frequency distribution of diagnostic subspecific SNPs.
Figure 2: SNP discovery bias.
Figure 3: Regions of intersubspecific introgression in the reference strains.
Figure 4: Subspecific origin of classical and hybrid strains.
Figure 5: Frequency distribution of the normalized variation in pairwise comparisons between classical strains.
Figure 6: Frequency and spatial distributions of the mean normalized genetic variation observed among 11 resequenced strains.

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Acknowledgements

We thank S. Ahmed for technical assistance; K. Paigen, K. Broman and B. Payseur for helpful comments during the preparation of the manuscript; J. Felsenstein for advice and L. Wu for assistance with the phylogenetic tree computations and A. Smith for developing a genome browser format for displaying phylogenetic trees. CIM/Pas was provided by F. Bonhomme (University Mont Pellier II). This work was supported by the US National Institute of General Medical Sciences as part of the Center of Excellence in Systems Biology (1P50 GM076468).

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This study was designed by F.P.-M.V. and G.A.C. The genome-wide analyses were carried out by H.Y. The sequence data used to determine the false-negative and false-positive rates and to confirm the presence and direction of intrasubspecific introgression were generated by T.A.B.

Corresponding author

Correspondence to Fernando Pardo-Manuel de Villena.

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The authors declare no competing financial interests.

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Supplementary Figures 1–6, Supplementary Note, Supplementary Table 1 (PDF 3338 kb)

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Yang, H., Bell, T., Churchill, G. et al. On the subspecific origin of the laboratory mouse. Nat Genet 39, 1100–1107 (2007). https://doi.org/10.1038/ng2087

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