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

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

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Item Permalink: http://hdl.handle.net/11858/00-001M-0000-000F-D5B4-4 Version Permalink: http://hdl.handle.net/11858/00-001M-0000-000F-D5B5-2
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 Creators:
Scavetta, Rick J.1, Author              
Tautz, Diethard1, Advisor              
Leptin, Maria, Referee
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1Department Evolutionary Genetics, Max Planck Institute for Evolutionary Biology, Max Planck Society, ou_1445635              

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 Abstract: 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.

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Language(s): eng - English
 Dates: 2009-05-25
 Publication Status: Accepted / In Press
 Pages: XVII, 77 Bl.
 Publishing info: Köln : Universität Köln
 Table of Contents: Table of Contents
Dedication .......................................................................................................... i
Epigraph ........................................................................................................... iii
List of Tables and Figures ................................................................................... vii
List of Abbreviations ........................................................................................... ix
Acknowledgments ............................................................................................... xi
Zusammenfassung ............................................................................................. xiii
Abstract ............................................................................................................xv
De claration...................................................................................................... xvii
1.0 Introduction .............................................................................................. 1
1.1 Mus musculus ssps.: A Model for Evolutionary Gene tics ............................ 1
1.1.1 The Origins of Mus musculus ssps. ...................................................... 1
1.2 A Portrait of Copy Number Variation .................................................. 3
1.2.1 The Genomic Landsc ape of Copy Number Variation ........................... 3
1.2.2 Cons equenc es of Copy Number Variation ......................................... 5
1.2.3 The Origin of Copy Number Variations ............................................ 7
1.3 Gene tic Divergence and Reproduc tive Isolation ................................... 11
1.3.1 Spe ciation Genetics of Mus musculus ssps. ......................................... 11
1.3.2 The Xlr Superfamily ..................................................................... 13
1.4 The Aim and Relevanc e of this study.................................................. 15
2.0 CNV De stabilization Mus musculus ssp. Hybrids ............................................. 17
2.1 The Slx Gene Family........................................................................ 17
2.1.1 Genomic Architec ture ................................................................... 17
2.1.2 Variation in Slx cDNA .................................................................. 18
2.2 CNV De stabilizations in Intersubspecific Hybrids ............................... 21
2.2.1 CNVs in Wild Populations ............................................................. 21
2.2.2 CNVs in Wild Hybrid Populations .................................................. 25
2.3 CNVs in Laboratory-Bred Hybrids .................................................... 31
2.3.1 CNVs in the F1 and F2 Generation ................................................. 31
2.3.2 De te c tion of CNV Des tabilization by aCGH ................................... 36
2.4 Discussion ..................................................................................... 40
3.0 DNA Repair Pathways in Hybrid Mice .......................................................... 43
3.1 Genome Maintenanc e and Instability ................................................. 43
3.2 Organogenesis and Genome Maintenanc e ........................................... 44
3.3 Experimental Outline ...................................................................... 45
3.4 A Description of Embryonic DNA Repair Pathways ............................. 49
3.5 Discussion ..................................................................................... 56
4.0 Concluding Remarks ................................................................................. 61
4.1 A General Summary ........................................................................ 61
4.2 Novel Alleles and Hybrid Spe ciation .................................................. 61
4.3 Outloo k ........................................................................................ 62
5.0 Materials & Methods ................................................................................. 63
6.0 Re ferenc es ............................................................................................... 67
7.0 Lebenslauf ............................................................................................... 79
 Rev. Type: -
 Identifiers: eDoc: 457049
Other: Diss/12201
 Degree: PhD

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