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Copy number variants and selective sweeps in natural populations of the house mouse (Mus musculus domesticus).

Bryk J, Tautz D - Front Genet (2014)

Bottom Line: Roughly two thirds of all CNVs found were deletions.We found no enrichment of CNVs among the differentially expressed genes between the populations compared to the invariant ones, nor any meaningful correlation between CNVs and gene expression changes.Among the CNV genes, we found cellular component gene ontology categories of the synapse overrepresented among all the 2444 genes tested.

View Article: PubMed Central - PubMed

Affiliation: Max Planck Institute for Evolutionary Biology Plön, Germany.

ABSTRACT
Copy-number variants (CNVs) may play an important role in early adaptations, potentially facilitating rapid divergence of populations. We describe an approach to study this question by investigating CNVs present in natural populations of mice in the early stages of divergence and their involvement in selective sweeps. We have analyzed individuals from two recently diverged natural populations of the house mouse (Mus musculus domesticus) from Germany and France using custom, high-density, comparative genome hybridization arrays (CGH) that covered almost 164 Mb and 2444 genes. One thousand eight hundred and sixty one of those genes we previously identified as differentially expressed between these populations, while the expression of the remaining genes was invariant. In total, we identified 1868 CNVs across all 10 samples, 200 bp to 600 kb in size and affecting 424 genic regions. Roughly two thirds of all CNVs found were deletions. We found no enrichment of CNVs among the differentially expressed genes between the populations compared to the invariant ones, nor any meaningful correlation between CNVs and gene expression changes. Among the CNV genes, we found cellular component gene ontology categories of the synapse overrepresented among all the 2444 genes tested. To investigate potential adaptive significance of the CNV regions, we selected six that showed large differences in frequency of CNVs between the two populations and analyzed variation in at least two microsatellites surrounding the loci in a sample of 46 unrelated animals from the same populations collected in field trappings. We identified two loci with large differences in microsatellite heterozygosity (Sfi1 and Glo1/Dnahc8 regions) and one locus with low variation across the populations (Cmah), thus suggesting that these genomic regions might have recently undergone selective sweeps. Interestingly, the Glo1 CNV has previously been implicated in anxiety-like behavior in mice, suggesting a differential evolution of a behavioral trait.

No MeSH data available.


Overview of the experimental design.
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Figure 1: Overview of the experimental design.

Mentions: Our subject are allopatric populations of the house mouse Mus musculus domesticus, from the Massif Central in France and around Cologne/Bonn area in Germany that diverged less than 3000 years ago (Cucchi et al., 2005); details of the populations and trappings are published in Ihle et al. (2006). We previously analyzed gene expression patterns in animals from both populations (Bryk et al., 2013) and decided to use gene expression differences as a proxy for identification of CNVs. Our hypothesis was that since CNVs are known to affect gene expression levels, we may enrich for CNVs by using genes for which we detected differences in gene expression between the two populations. To test the alternative hypothesis that gene expression differences are not a good predictor for CNVs, we also used genes with invariant expression across the two populations in the screen. A schematic overview of the experimental approach is shown on Figure 1.


Copy number variants and selective sweeps in natural populations of the house mouse (Mus musculus domesticus).

Bryk J, Tautz D - Front Genet (2014)

Overview of the experimental design.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4042557&req=5

Figure 1: Overview of the experimental design.
Mentions: Our subject are allopatric populations of the house mouse Mus musculus domesticus, from the Massif Central in France and around Cologne/Bonn area in Germany that diverged less than 3000 years ago (Cucchi et al., 2005); details of the populations and trappings are published in Ihle et al. (2006). We previously analyzed gene expression patterns in animals from both populations (Bryk et al., 2013) and decided to use gene expression differences as a proxy for identification of CNVs. Our hypothesis was that since CNVs are known to affect gene expression levels, we may enrich for CNVs by using genes for which we detected differences in gene expression between the two populations. To test the alternative hypothesis that gene expression differences are not a good predictor for CNVs, we also used genes with invariant expression across the two populations in the screen. A schematic overview of the experimental approach is shown on Figure 1.

Bottom Line: Roughly two thirds of all CNVs found were deletions.We found no enrichment of CNVs among the differentially expressed genes between the populations compared to the invariant ones, nor any meaningful correlation between CNVs and gene expression changes.Among the CNV genes, we found cellular component gene ontology categories of the synapse overrepresented among all the 2444 genes tested.

View Article: PubMed Central - PubMed

Affiliation: Max Planck Institute for Evolutionary Biology Plön, Germany.

ABSTRACT
Copy-number variants (CNVs) may play an important role in early adaptations, potentially facilitating rapid divergence of populations. We describe an approach to study this question by investigating CNVs present in natural populations of mice in the early stages of divergence and their involvement in selective sweeps. We have analyzed individuals from two recently diverged natural populations of the house mouse (Mus musculus domesticus) from Germany and France using custom, high-density, comparative genome hybridization arrays (CGH) that covered almost 164 Mb and 2444 genes. One thousand eight hundred and sixty one of those genes we previously identified as differentially expressed between these populations, while the expression of the remaining genes was invariant. In total, we identified 1868 CNVs across all 10 samples, 200 bp to 600 kb in size and affecting 424 genic regions. Roughly two thirds of all CNVs found were deletions. We found no enrichment of CNVs among the differentially expressed genes between the populations compared to the invariant ones, nor any meaningful correlation between CNVs and gene expression changes. Among the CNV genes, we found cellular component gene ontology categories of the synapse overrepresented among all the 2444 genes tested. To investigate potential adaptive significance of the CNV regions, we selected six that showed large differences in frequency of CNVs between the two populations and analyzed variation in at least two microsatellites surrounding the loci in a sample of 46 unrelated animals from the same populations collected in field trappings. We identified two loci with large differences in microsatellite heterozygosity (Sfi1 and Glo1/Dnahc8 regions) and one locus with low variation across the populations (Cmah), thus suggesting that these genomic regions might have recently undergone selective sweeps. Interestingly, the Glo1 CNV has previously been implicated in anxiety-like behavior in mice, suggesting a differential evolution of a behavioral trait.

No MeSH data available.