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キーワード:
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要旨:
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.