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Genomic destabilization at copy number variable loci in intersubspecific hybrids of Mus musculus ssps.


Scavetta,  Rick J.
Department Evolutionary Genetics, Max Planck Institute for Evolutionary Biology, Max Planck Society;

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Scavetta, R. J. (2009). Genomic destabilization at copy number variable loci in intersubspecific hybrids of Mus musculus ssps. PhD Thesis, Universität Köln, Köln.

Cite as: https://hdl.handle.net/11858/00-001M-0000-000F-D5B4-4
Copy number variation (CNV) contributes significantly to natural genetic variation within and between populations. However, the mutational mechanisms leading to copy number variation, as well as the processes that control the size of CNV regions are so far not well understood. This thesis deals with CNVs containing X- and Y-linked members of a large gene family in Mus musculus ssps. The phenomenon that CNV regions show dramatic copy number amplifications in intersubspecific hybrids of M. m. domesticus and M. m. musculus is described. This is observed in natural and laboratorybred hybrids. Extreme copy number amplification, not found in wild-caught hybrids, can be generated under laboratory conditions, suggesting that there is a selection against this CNV destabilization phenomenon in the wild. Specific analysis of hybrid males indicates that neither meiotic recombination nor inter-chromosomal exchange is required for this to occur, suggesting intrachromosomal (i.e. sister chromatid) exchange that can occur at an elevated frequency in intersubspecific crosses. As confirmation, I can detect a greater number of somatic CNVs between organs in hybrid individuals than pure-breds and disruptions in DNA repair pathways known to regulate sister chromatid exchange also appear to be misregulated in some hybrids. It appears that the relative stability of CNV loci in pure-breeding populations can be disrupted in crosses with animals from another population, and this relies on mutational mechanisms acting during development. This finding offers a unique perspective on reproductive isolation and may be important for understanding the build-up of genetic incompatibilities between these subspecies.