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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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Multiple QTL map of F2 variation in mean MLH1 foci count.The subset of chromosomes with significant QTL is shown, with the positions of genotyped markers denoted by ticks along the x-axis.
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pgen-1002116-g005: Multiple QTL map of F2 variation in mean MLH1 foci count.The subset of chromosomes with significant QTL is shown, with the positions of genotyped markers denoted by ticks along the x-axis.

Mentions: Single QTL mapping approaches, including standard interval mapping, formally assume that only one QTL in the genome affects the phenotype. When QTL of moderate to large effect exist, accounting for the phenotypic variance they explain can enhance statistical power to find additional loci. The discovery of the major effect QTL on the X chromosome prompted us to use an approach that could adjust for the presence of this locus to enable the simultaneous detection of multiple additional QTL. We applied a model-based multiple QTL mapping strategy [56] to identify the set of genetic loci that best explain segregating variation in mean MLH1 foci count among F2 males. Using a forward/backward model selection approach, with model discrimination performed via penalized LOD scores to control the rate of false inclusion [57], we identify six autosomal QTL and two X-linked QTL for genomic recombination rate (Figure 5). As expected, the two QTL identified in the single QTL scan are among those recovered in the multiple QTL mapping analysis.


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

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

Multiple QTL map of F2 variation in mean MLH1 foci count.The subset of chromosomes with significant QTL is shown, with the positions of genotyped markers denoted by ticks along the x-axis.
© Copyright Policy
Related In: Results  -  Collection

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

pgen-1002116-g005: Multiple QTL map of F2 variation in mean MLH1 foci count.The subset of chromosomes with significant QTL is shown, with the positions of genotyped markers denoted by ticks along the x-axis.
Mentions: Single QTL mapping approaches, including standard interval mapping, formally assume that only one QTL in the genome affects the phenotype. When QTL of moderate to large effect exist, accounting for the phenotypic variance they explain can enhance statistical power to find additional loci. The discovery of the major effect QTL on the X chromosome prompted us to use an approach that could adjust for the presence of this locus to enable the simultaneous detection of multiple additional QTL. We applied a model-based multiple QTL mapping strategy [56] to identify the set of genetic loci that best explain segregating variation in mean MLH1 foci count among F2 males. Using a forward/backward model selection approach, with model discrimination performed via penalized LOD scores to control the rate of false inclusion [57], we identify six autosomal QTL and two X-linked QTL for genomic recombination rate (Figure 5). As expected, the two QTL identified in the single QTL scan are among those recovered in the multiple QTL mapping analysis.

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