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Genetic analysis of genome-scale recombination rate evolution in house mice.

Dumont BL, Payseur BA - PLoS Genet. (2011)

Bottom Line: Much of the F2 variance for recombination rate and a substantial portion of the difference in recombination rate between the parental strains is explained by eight moderate- to large-effect quantitative trait loci, including two transgressive loci on the X chromosome.In contrast to the rapid evolution observed in males, female CAST/EiJ and PWD/PhJ animals show minimal divergence in recombination rate (∼5%).The existence of loci on the X chromosome suggests a genetic mechanism to explain this male-biased evolution.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Genetics, University of Wisconsin, Madison, Wisconsin, United States of America.

ABSTRACT
The rate of meiotic recombination varies markedly between species and among individuals. Classical genetic experiments demonstrated a heritable component to population variation in recombination rate, and specific sequence variants that contribute to recombination rate differences between individuals have recently been identified. Despite these advances, the genetic basis of species divergence in recombination rate remains unexplored. Using a cytological assay that allows direct in situ imaging of recombination events in spermatocytes, we report a large (∼30%) difference in global recombination rate between males of two closely related house mouse subspecies (Mus musculus musculus and M. m. castaneus). To characterize the genetic basis of this recombination rate divergence, we generated an F2 panel of inter-subspecific hybrid males (n = 276) from an intercross between wild-derived inbred strains CAST/EiJ (M. m. castaneus) and PWD/PhJ (M. m. musculus). We uncover considerable heritable variation for recombination rate among males from this mapping population. Much of the F2 variance for recombination rate and a substantial portion of the difference in recombination rate between the parental strains is explained by eight moderate- to large-effect quantitative trait loci, including two transgressive loci on the X chromosome. In contrast to the rapid evolution observed in males, female CAST/EiJ and PWD/PhJ animals show minimal divergence in recombination rate (∼5%). The existence of loci on the X chromosome suggests a genetic mechanism to explain this male-biased evolution. Our results provide an initial map of the genetic changes underlying subspecies differences in genome-scale recombination rate and underscore the power of the house mouse system for understanding the evolution of this trait.

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Results of single QTL mapping for F2 variation in mean MLH1 foci count.The LOD curve for each autosome and the X chromosome is displayed. The horizontal red (blue) line corresponds to the autosomal (X chromosome) significance threshold obtained by permutation with α = 0.05. Positions of genotyped markers are indicated by ticks along the x-axis.
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pgen-1002116-g004: Results of single QTL mapping for F2 variation in mean MLH1 foci count.The LOD curve for each autosome and the X chromosome is displayed. The horizontal red (blue) line corresponds to the autosomal (X chromosome) significance threshold obtained by permutation with α = 0.05. Positions of genotyped markers are indicated by ticks along the x-axis.

Mentions: We genotyped our F2 population at 222 informative SNPs distributed across the genome. Using standard interval mapping [54] with a permutation-derived threshold for declaring statistical significance (genome-wide α = 0.05) [55], we identified two genomic regions linked to variation in mean MLH1 foci count. One of these QTL localizes to the proximal half of chromosome 7 and the second QTL lies on the X chromosome (Figure 4). Although there is a clear peak in the X chromosome LOD profile centered on ∼30 cM, the entire chromosome displays strong statistical evidence for linkage to variation in global recombination rate (Figure 4). QTL genotype at this single, large-effect locus explains 46% of the variance in mean MLH1 foci count among F2 males (adjusted R2 = 0.46 from a linear regression).


Genetic analysis of genome-scale recombination rate evolution in house mice.

Dumont BL, Payseur BA - PLoS Genet. (2011)

Results of single QTL mapping for F2 variation in mean MLH1 foci count.The LOD curve for each autosome and the X chromosome is displayed. The horizontal red (blue) line corresponds to the autosomal (X chromosome) significance threshold obtained by permutation with α = 0.05. Positions of genotyped markers are indicated by ticks along the x-axis.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3111479&req=5

pgen-1002116-g004: Results of single QTL mapping for F2 variation in mean MLH1 foci count.The LOD curve for each autosome and the X chromosome is displayed. The horizontal red (blue) line corresponds to the autosomal (X chromosome) significance threshold obtained by permutation with α = 0.05. Positions of genotyped markers are indicated by ticks along the x-axis.
Mentions: We genotyped our F2 population at 222 informative SNPs distributed across the genome. Using standard interval mapping [54] with a permutation-derived threshold for declaring statistical significance (genome-wide α = 0.05) [55], we identified two genomic regions linked to variation in mean MLH1 foci count. One of these QTL localizes to the proximal half of chromosome 7 and the second QTL lies on the X chromosome (Figure 4). Although there is a clear peak in the X chromosome LOD profile centered on ∼30 cM, the entire chromosome displays strong statistical evidence for linkage to variation in global recombination rate (Figure 4). QTL genotype at this single, large-effect locus explains 46% of the variance in mean MLH1 foci count among F2 males (adjusted R2 = 0.46 from a linear regression).

Bottom Line: Much of the F2 variance for recombination rate and a substantial portion of the difference in recombination rate between the parental strains is explained by eight moderate- to large-effect quantitative trait loci, including two transgressive loci on the X chromosome.In contrast to the rapid evolution observed in males, female CAST/EiJ and PWD/PhJ animals show minimal divergence in recombination rate (∼5%).The existence of loci on the X chromosome suggests a genetic mechanism to explain this male-biased evolution.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Genetics, University of Wisconsin, Madison, Wisconsin, United States of America.

ABSTRACT
The rate of meiotic recombination varies markedly between species and among individuals. Classical genetic experiments demonstrated a heritable component to population variation in recombination rate, and specific sequence variants that contribute to recombination rate differences between individuals have recently been identified. Despite these advances, the genetic basis of species divergence in recombination rate remains unexplored. Using a cytological assay that allows direct in situ imaging of recombination events in spermatocytes, we report a large (∼30%) difference in global recombination rate between males of two closely related house mouse subspecies (Mus musculus musculus and M. m. castaneus). To characterize the genetic basis of this recombination rate divergence, we generated an F2 panel of inter-subspecific hybrid males (n = 276) from an intercross between wild-derived inbred strains CAST/EiJ (M. m. castaneus) and PWD/PhJ (M. m. musculus). We uncover considerable heritable variation for recombination rate among males from this mapping population. Much of the F2 variance for recombination rate and a substantial portion of the difference in recombination rate between the parental strains is explained by eight moderate- to large-effect quantitative trait loci, including two transgressive loci on the X chromosome. In contrast to the rapid evolution observed in males, female CAST/EiJ and PWD/PhJ animals show minimal divergence in recombination rate (∼5%). The existence of loci on the X chromosome suggests a genetic mechanism to explain this male-biased evolution. Our results provide an initial map of the genetic changes underlying subspecies differences in genome-scale recombination rate and underscore the power of the house mouse system for understanding the evolution of this trait.

Show MeSH